- Mode of origin : Genes having only two distinct alleles. If mutation occurs in the same gene but in different directions in different individuals, the population as a whole will have many different alleles of that gene. Each allele may produce a different phenotype, and various combinations of alleles produce several genotypes and phenotypes in the
- There are more than two alleles of the same
- All multiple alleles occupy the corresponding loci in the homologous
- A chromosome or a gamete has only one allele of the
- Any one individual contains only two of the different alleles of a gene, one on each chromosome of the homologous pair carrying that
- Multiple alleles express different alternative of a single
- Different alleles may show codominance, dominance-recessive behaviour or incomplete dominance among
- Multiple alleles confirm to the Mendelian pattern of
- Definition : More than two alternative forms (alleles) of a gene in a population occupying the same locus on a chromosome or its homologue are known as multiple
- Examples of multiple allelism : A well known example of a trait determined by multiple alleles is the blood groups in man and skin colour.
Blood groups in man
- Blood proteins : According to Karl landsteiner (1900) a Nobel prize winner, blood contains two types of proteinous substances due to which agglutinations
- Agglutinogen or antigen : It is a protein found on the cell membrane of RBC’s.
- Agglutinin or antibody : This the other proteinous substance, found in the plasma of the
Whenever the blood of a person receives the foreign proteins (antigen) his blood plasma starts forming the antibodies in order to neutralize the foreign antigens.
- Agglutinations : Two types of antigens are found on the surface of red blood corpuscles of man, antigen A and B. To react against these antigens two types of antibodies are found in the blood plasma which are accordingly known as antibody – anti-A or a and anti-B or b. Agglutination takes place only when antigen A and antibody a occur together or antigen B and antibody b are present in the blood. Under such condition antibody a reacts with antigen A and makes it highly Similarly antigen B in presence of antibody b become highly sticky with the result RBC’s containing these antigens clump to form a bunch causing blockage of the capillaries. Agglutination in blood is therefore antigen-antibody reaction.
(c) Types of blood groups
- ABO blood group : Landsteiner divided human population into four groups based on the presence of antigens found in their red blood Each group represented a blood group. Thus there are four types of blood groups viz. A, B, AB and O. He observed that there was a reciprocal relationship between antigen and antibody according to which a person has antibodies for those antigens which he does not possess. For example a person of blood group B does not possess antigen A but his blood plasma has antibody ‘a’ due to which agglutination with the blood of a person with blood group A occurs. Similarly persons with blood group AB possess both the antigens A and B but their blood plasma does not possess any of the antibodies. In the same way person
having blood group A does not possess antigen B but antibody ‘b’ is found in his blood plasma. Persons with blood group O possess none of the antigens and that is why their blood possesses both the antibodies ‘a’ and ‘b’.
Blood groups of man with antigen and antibodies
|Antigen||Antibody||Type of blood group||% in society|
|(1) A||Anti-B or ‘b’||A||23.5|
|(2) B||Anti-A or ‘a’||B||34.5|
|(3) A, B||Absent||AB||7.5|
|(4) None||‘a’ and ‘b’||O||34.5|
- M, N blood group : Landsteiner and A.S. Wiener discovered that antigen M,N or both MN are also found on the surface of red blood corpuscles of human beings. No antibodies are however formed in the blood plasma for these antigens. If however, these antigens are injected into rabbit’s blood, they produced such antibodies which are not found in human beings. Inheritance of such kind of blood groups is also brought about like that of A, B and AB.
In this way when blood with M group is injected in rabbit it will produce antibodies in the blood serum which will bring about agglutination with blood group M and MN but not with blood of N group. In the same way on injecting blood of N group into the rabbit it will bring about agglutination with blood group N and MN and not with blood having blood group M.
- Blood transfusion : Blood transfusion is best done in the persons of same blood At the same time it is possible to know in which different blood groups the blood transfusion can be made possible.
Persons with blood group AB are called universal recipients because both antigens A and B are found in their blood and the two antibodies ‘a’ and ‘b’ are absent. Therefore, such persons can receive blood of all the blood groups. In the same way persons who have blood group O– are universal donors as they lack both the antigens and Rh– person can donate to Rh+ person as well as Rh– person but Rh+ person cannot donate blood to Rh– person. But at the same time such persons can not be given the blood of any other blood group except blood group O because their blood possesses both the antibodies ‘a’ and ‘b’. Persons belonging to blood group A and B contain only one antigen and one antibody against it, in their blood. Such persons can therefore receive blood either of the blood group of their own or the blood group O.
Possibilities of blood transfusion
|Blood group||Can accept from||Can donate to||Agglutination||Specific mention|
|(1) A||A, O||A, AB||No||Yes||No||Yes|
|(2) B||B, O||B, AB||Yes||No||No||Yes|
|(3) AB||A, B, AB, O||AB only||Yes||Yes||No||Yes||Universal recipient|
|(4) O||O only||A, B, AB, O||No||No||No||No||Universal donor|
- Blood bank : A place where blood of different blood groups is safely stored in bottles for emergency use, is called blood Blood after proper testing is stored in a sealed bottle at a definite temperature (4°-6°c) to be preserved for a definite time period.
Artificial anticoagulants are used to prevent blood clotting in the blood banks. These anticoagulants are added to the blood preserved in bottle. Such anticoagulants include sodium citrate, double oxalates (sodium and ammonium), dicumarol and EDTA (ethylene diamine tetra acetic acid). The whole blood in this way can be stored for a maximum period of 21 days.
- Inheritance of blood groups : Blood groups in human are inheritable trait and are inherited from parents to offsprings on the basis of Mendel’s Blood group inheritance depends on genes received from
parents. Genes controlling blood group in man are three instead of two and are called multiple alleles. All these three genes or alleles are located on the same locus on homologous chromosomes. A person can have only two of these three genes at a time which may be either similar or dissimilar in nature. These genes control the production of blood group/antigens in the offspring. The gene which produces antigen A is denoted by Ia, gene for antigen B by Ib and the gene for the absence of both antigens by Io. it is customary to use the letter I (Isohaemagglutinogen) as a basic symbol for the gene at a locus. Based on this, six genotypes are possible for four blood groups in human population.
Genotype of blood groups in man.
|Genotype||Nature of gene||Type of blood group|
The alleles Ia and Ib of human blood group are said to be codominant because both are expressed in the phenotype AB. Each produces its antigen and neither checks the expression of the other. There is codominance as well as dominant recessive inheritance in the case of the alleles for the blood groups in human beings. The alleles Ia and Ib are codominant and are dominant over the allele Io (Ia = Ib > Io). The human blood groups illustrate both multiple allelism and codominance. This blood group are inherited in the simple Mendelian fashion. Thus offsprings with all four kinds of blood groups are possible. If the parents are heterozygous for blood groups A and B which is shown below.
Cross between parents heterozygous for blood group A and B
Male (Heterozygous for blood group A)
Gametes Ia Io
|Female (Heterozygous for blood group
|Ib||Ia Ib||Ib Io|
|Group AB||Group B|
|Io||Ia Io||Io Io|
|Group A||Group O|
If we know the blood groups of a couple the blood groups of their children can easily be predicted as shown below.
Possible blood groups of children for known blood groups of parents.
|Blood groups of parents (known)||Genotype of parents (known)||Blood groups of children|
|(1)||O and O||Io Io ´ Io Io||O||A, B, AB|
|(2)||O and A||Io Io ´ Ia Io||O, A||B, AB|
|(3)||A and A||Ia Io ´ Ia Io||O, A||B, AB|
|(4)||O and B||Io Io ´ Ib Io||O, B||A, AB|
|(5)||B and B||Ib Io ´ Ib Io||O, B||A, AB|
|(6)||A and B||Ia Ia ´ Ib Ib Ia Ia ´ Ib Io
Ia Io ´ Ib Io
O, A, B, AB
|(7)||O and AB||Io Io ´ Ia Ib||A, B||O, AB|
|(8)||A and AB||Ia Io ´ Ia Ib||A, B, AB||O|
|(9)||B and AB||Ib Io ´ Ia Ib||A, B, AB||O|
|(10)||AB and AB||Ia Ib ´ Ia Ib||A, B, AB||O|
- Significance of blood groups : The study of blood groups is important in settling the medico-legal cases of disputed parentage because with the help of blood group of a child it can be decided as to who can be his or her genuine father, if the blood group of mother is known. It means that blood groups of the mother and a child being known, the possibilities of blood group in the father can be worked out or if blood group of child and that of father is known then that of mother can be known with the help of the table given Blood groups can also save an innocent from being hanged in the case of murder and can help in hanging the real culprit.
Possibilities of blood groups of other parent on the basis of blood group of child and one parent being known.
|S.No.||Blood group of child (known)||Genotype of child (known)||Blood group of father or mother (known)||Blood group of other parent|
|(1)||O||Io Io||O A
|(2)||A||Ia Io, Ia Ia||O, B||A, AB||O, B|
|(3)||B||Ib Io , Ib Ib||O, A
A, B, AB
- Rhesus or Rh factor
- Rh factor : Landsteiner and Weiner (1940) discovered a different type of protein in the blood of Rhesus monkey. They called it Rh antigen or Rh factor after Rhesus monkey. When injected the blood of these monkeys into the blood of guinea pigs they noticed the formation of antibodies against the Rh antigen in the blood of guinea Formation of Rh antigen is controlled by dominant gene (R) and its absence by recipient gene (r). People having this antigen with genotype (RR or Rr) are called Rh positive (Rh+) and those whose blood is devoid of it with genotype (rr) are Rh negative (Rh–). About 85% human beings in Europe and 97% in India are Rh+.
- Importance of Rh factor : Generally human blood is devoid of Rh antibodies. But it has been noticed that on transfusion of blood of a Rh+ person to Rh– person, the recepient develops Rh antibodies in its blood If Rh+ blood is transfused for the second times it causes agglutination and leads to the death of Rh– person.
- Erythroblastosis foetalis : This disease is related to the birth of a child related with Rh It causes the death of the foetus within the womb or just after birth. It was studies by Levine together with Landsteiner and Wiener. The father of Rh affected foetus is Rh+ and the mother is Rh–. The child inherits the Rh+ trait from the father. A few Rh+ red blood corpuscles of foetus in the womb enter in the blood of the mother where they develop
Rh antibodies. As mother’s blood is Rh– i.e. devoid of Rh antigen, it causes no harm to her. These Rh antibodies alongwith the mother’s blood on reaching the foetal circulation cause clamping of foetal RBCs or agglutination reaction. The first child is some how born normal because by that time the number of antibodies in mother’s blood remain lesser but they increase with successive pregnancies. Thus the foetus following the first child dies either within the womb or just after its birth. This condition is known as erythroblastosis foetalis. So a marriage between Rh+ boy and Rh– girl is considered biologically incompatible.
Type of biological marriage on the basis of Rh factor
|Boy||Girl||Type of biological marriage|
However, there is no danger if both parents are Rh– or mother is Rh+ and father is Rh–. Rh factor serum has been developed which when given to the Rh– mother after each child birth saves the next child. This serum contains Rh antibodies which destroy the Rh antigens of foetus before they can initiate formation of Rh antibodies in the mother.
RR X rr Rr
Rh antibodies formed
First pregnancy child survives
Rh-positive second pregnancy foetus dies
Rh positive erythrocytes (antigens) of foetus enter maternal circulation and stimulate production of Rh antibodies
Antibodies of mother enter foetal circulation (subsequent pregnancies) and destroy foetal erythrocytes causing erthroblastosis or death
Fig : Foetal death in the womb due to erythroblastosis foetalis
- Rhogam method : It is a method of preventing erythroblastosis foetalis. In this method the Rh– mother is given a special blood test after delivery of her Rh+ If foetal Rh+ cells are present in mother’s blood. She is given injections of rhogam. Rhogam is a preparation of anti-Rh antibodies. It is obtained from immunized donors. The rhogam forms a coat around foetal RBCs in mother’s blood. As a result no Rh+ antigens are available to stimulate mother’s circulation and no antibodies are formed.
- Inheritance of Rh factor : Rh factor or Rh antigen is determined by a series of four pair of multiple They are denoted as R1, R2, R0, Rz, r’, r”, ry and r. The alleles denoted by capital letter give rise to Rh+
condition while those denoted by small letter to Rh– condition. Rh+ condition is dominant over Rh– condition. Thus Rh+ person may be homozygous (RR) or heterozygous (Rr) while Rh– persons are always homozygous(rr). Hereditary trait for Rh– factor is inherited according to Mendelian principle.
Homozygous Homozygous Heterozygous Heterozygous
RR rr Rr
R R ×
r r × R r ×
Rr Rr rr
Fig : Inheritance of Rh antigen
- Most common blood groups in India are B and Rh+.
- Best recipient is AB+.
- The AB blood group was discovered by two Landsteiner’s students Von Decastello and Sturli (1902).
- Inheritance of A, B, AB and O blood types in man was discovered by Bernstein in 1925.
- A very rare h/h individual are like blood type O They are said to have the Bombay blood type.
- Rh factor was first of all reported in RBCs of Macaca rhesus (rhesus monkey) by Landsteiner and Wiener in
- Immunological incompatibility between mother and foetus sometimes results in a condition called haemolytic disease of the new born (HDN).
- HDN was earlier known as erythroblastosis
The idea of mutation first originated from the observations of a Dutch botanist Hugo de Vries (1880) on variations in plants of Oenothera lamarckiana. The mutation can be defined as sudden, stable discontinuous and inheritable variations which appear in organism due to permanent change in their genotype. Mutation is mainly of two types :
- Spontaneous mutations : Mutation have been occurring in nature without a known cause is called spontaneous
- Induced mutation : When numerous physical and chemical agents are used to increase the frequency of mutations, they are called induced
- Gene mutations : Gene or point mutations are stable changes in genes e. DNA chain. Many times a change in a gene or nucleotide pair does not produce detectable mutation. Thus the point or gene mutation mean the process by which new alleles of a gene are produced. The gene mutation are of following types
- Tautomerism : The changed pairing qualities of the bases (pairing of purine with purine and pyrimidine with pyrimidine) are due to phenomenon called
Tautomeres are the alternate forms of bases and are produced by rearrangements of electrons and proton in
4 1 N
N 2 N
3 2 N
N 4 1 N
4 1 NH
Fig : Few tautomers
Tautomerism is caused by certain chemical mutagens. In the next replication purines pair with pyrimidines and the base pair is altered at a particular locus. The uncommon forms are unstable and at the next replication, cycle revert back to their normal forms.
- Substitutions (Replacements) : These are gene mutations where one or more nitrogenous base pair are changed with others. It may be further of three sub
- Transition : In transition, a purine (adenine or guanine) or a pyrimidine (cytosine or thymine or uracil) in triplet code of DNA or mRNA is replaced by its type e. a purine replaces purine and pyrimidine replaces pyrimidine.
A T G C T G G T
II II III III II III III II Original DNA
T A C G A C C A 1 2 3 4 5 6 7 8
1 2 3 4 5 6 7 8
- Transversion : Transversion are substitution gene mutation in which a purine (adenine or guanine) is replaced by pyrimidine (thymine or cytosine) or vice versa.
DNA base sequence cytosine
m RNA base sequence guanine
Specific amino acid
Adenine substituted for thymine
Fig : Transversion
- Frame shift mutations : In this type of mutations addition or deletion of single nitrogenous base takes place. None of the codon remains in the same original position and the reading of genetic code is shifted laterally either in the forward or backward
TAC CAT TAG ATT
Base triplet in DNA
Insertion of ‘C’ Deletion of ‘T’
TAC CCA TTA GAT T TAC CAT AGA TT
Fig : Frame shift mutations
- Chromosomal mutation or aberrations : A gene mutation normally alters the information conveyed by a gene, it alters the message. On the other hand, chromosomal mutation only alters the number or position of existing genes. They may involve a modification in the morphology of chromosome or a change in number of
Morphological aberrations of chromosomes :
- Deletion or deficiency : Sometimes a segment of chromosome break off and get lost. Deficiency generally proves lethal or
- Deficiency : If a terminal segment of a chromosome is lost, it is called
- Deletion : If intercalary segment is lost it is termed
Deletions in human beings
- A missing chromosome segment is referred to either as deletion or
- In a dilpoid organism, the deletion of a chromosome segment makes the part of genome hypoploid.
- Deletion may be associated with phenotypic effect, especially if the it is
(1) Cri-du-chat Syndrome
- A classical example of deletion is the Cri-du-chat syndrome (from the french words for “cry of the cat”) in human beings discovered by Lejeune in
- This condition is caused by a conspicuous deletion in the short arm of one of the 5th
Fig : Cat cry syndrome (A) An infant (B) An older child
- These individuals are severely impaired, mentally as well as physically; their plaintive catlike crying gives the syndrome its
(2) Wolf-Hirschhorn’s Syndrome
- Wolf-Hirschhorn’s syndrome is another well characterized deletion syndrome in human beings caused by a deletion of short arm of chromosome 4 (4p-).
- The phenotypic effect includes wide-spaced eyes and cleft lip.
- Duplication : In this mutation deleted chromosomal segment is attached to its normal homologous Here a gene or many genes are repeated twice or more times in the same chromosome.
- Inversion : A piece of chromosome is removed and rejoined in reverse order. For example a chromosome with the gene order A, B, C, D, E, F, G, H is broken between B,C,D and between f and g and the centre portion turned through 180°, the resulting gene order is A, D, C, B, E, F, G, H it is of two
- Pericentric inversion : The centromere lies within the inverse
- Paracentric inversion : The centromere lies outside the inverted
- Translocation : Mutual exchange (reciprocal) of the chromosome segments between non homologous An exchange of parts between two non homologous chromosomes is called reciprocal translocation. In simple translocation a segment of one chromosome breaks and is transferred to another non-homologous
A B C D E F G H
A B C D E F G H
A B C D E F G H
A B C D E F G H
A B C E F G H
A B C B C D E F G H
A D C B E F G H
M N O C D E F G H
M N O P Q R
Reciprocal Translocation D
A B P Q R
Fig : Types of chromosomal mutation
Translocations in human beings
- Certain types of cancer are associated with chromosome
- Two examples of tumours associated with consistent chromosome translocations are Chronic Myelogenous Leukaemia (CML) and burkitt’s
(1) Chronic Myelogenous Leukaemia (CML)
- Chronic myelogenous leukaemia in human beings is a fatal cancer involving uncontrolled replication of myeloblasts (stem cells of white blood cells).
- Ninety percent of CML is associated with an aberration of chromosome
- This abnormal chromosome was originally discovered in the city of Philadelphia in 1959 and thus is called the ‘Philadelphia chromosome’.
- Initially it was though to have a simple deletion in its long arm, however, subsequent analysis using molecular techniques has shown that the Philadelphia chromosome is actually the result of a reciprocal translocation between chromosomes 9 and 22.
- In the Philadelphia translocation, the tip of the long arm of chromosome 9 has been joined to the body of chromosome 22 and the distal portion of the long arm of chromosome 22 has been joined to the body of chromosome
- CML is characterized by an excess of granular leucocytes in the
- With the increase in the number of leucocytes, there is a reduction in the number of RBCs resulting in severe
(2) Burkitt’s Lymphoma
- Burkitt’s lymphoma, a particularly common disease in Africa, is another example of a white blood cell cancer associated with reciprocal translocations.
- These translocations invariably involve chromosome 8 and one of the three chromosomes (2, 14 and 22) that carry genes encoding the polypeptides that form immunoglobulins or
- Translocations involving chromosomes 8 and 14 are the most
Numerical aberrations of chromosomes : Each species has a characteristic number of chromosome.
Variations or numerical changes in chromosomes (Heteroploidy) can be mainly of two types:
Numerical changes in chromosomes
Polyploidy (3x,4x,5x,6x etc.)
(2n – 1)
(2n – 2)
(2n + 1)
(2n + 2)
Different kinds of numerical changes in chromosomes
(X = basic chromosome number, 2n = somatic chromosome number)
- Euploidy : The somatic chromosome number in euploids is the exact multiple of basic haploid number. In euploidy an organism acquires an additional set of chromosomes over and above the diploid
- Monoploidy or haploidy : Monoploids possess only one set or single basic set of chromosomes. Haploids on the other hand have half the somatic chromosome number. In diploid organisms monoploids and haploids are identical while in a tetra-or hexaploid with 4n or 6n chromosomes the haploids will possess 2n or 3n chromosome whereas its monoploid will possess only one set (n) of
- Diploidy : The common chromosome number in the somatic cells of plants and
- Polyploidy : Organism with more than two sets of chromosomes are known as polyploids. It may be triploid with three sets of chromosomes (3n) or tetraploid with four sets of chromosome (4n) and so
- Aneuploidy : Aneuploidy is the term applied for the chromosomal mutations involving only a part of a set, e., loss (hypoploidy) or addition (hyperploidy) of one or more chromosomes. Aneuploidy may result from non disjunction of chromosome during cell division.
- Monosomy : Diploid organism that are missing one chromosome of a single pair with genomic formula 2n – 1. Monosomics can form two kind of gametes, (n) and (n –1).
- Nullisomy : An organism that has lost a chromsome pair is nullisomic. The result is usually lethal to diploids (2n – 2).
- Trisomy : Diploids which have extra chromosome represented by the chromosomal formula 2n + 1. One of the pairs of chromosomes has an extra member, so that a trivalent may be formed during meiotic
- Tetrasomy : In tetrasomic individual particular chromosome of the haploid set is represented four times in a diploid chromosomal The general chromosomal formula for tetrasomics is 2n + 2 rather than 2n + 1+ 1. The formula 2n + 1 + 1 represents a double trisomic.
- Types of aneuploidy : Aneuploidy may be of following types on the basis of chromosomes involved in non
- Aneuploidy involving non-disjunction in sex chromosomes : This kind of aneuploidy is brought about due to non-disjunction in sex chromosomes. It may lead to following types of syndromes :
- Turner’s syndrome : Such persons are monosomic for sex chromosomes e. possess only one X and no Y chromosome (XO). In other words they have chromosome number 2n – 1 = 45. They are phenotypic females but are sterile because they have under developed reproductive organs. They are dwarf about 4 feet 10 inches and are flat chested with wide spread nipples of mammary glands which never enlarge like those in normal woman. They develop as normal female in childhood but at adolescence their ovaries remain under developed. They lack female hormone estrogen. About one out of every 5,000 female births results in Turner’s syndrome.
- Klinefelter’s syndrome : Since 1942, this abnormality of sex is known to geneticists and physicians. It occurs due to Trisomy of sex chromosomes which results in (XXY) sex chromosomes. Total chromosomes in such persons are 2n + 1 = 47 in place of 46. Klinefelter (1942) found that testes in such male remain under developed in They develop secondary sex characters of female like large breasts and loss of facial hair. Characters of male develop due to Y chromosome and those like female due to XX chromosomes. About one male child out of every 5,000 born, develops Klinefelter’s syndrome.
Such children are born as a result of fertilization of abnormal eggs (XX) by normal sperms with (X) or (Y) chromosomes or by fertilization of normal eggs with (X) chromosomes by abnormal sperms with (XY) chromosome. They are sterile males mentally retarded and are eunuchs.
- Super females and metasuper females : Presence of extra (X) chromosomes in females shows such condition leading to (XXX, XXXX, XXXXX), having total 47, 48 or 49 chromosomes in each Females with this type of aneuploidy show abnormal sexual development and mental retardation. Severeness of abnormality increases with the increase in number of (X) chromosomes.
- Criminal’s syndrome (super males) : Presence of an extra (Y) chromosome in males causes such a condition (XYY) resulting in individuals with 2n + 1 = 47 chromosomes. They have unusual height, mentally retarded and criminal bent of mind since birth. Their genital organs are under developed. Their frequency is one in every 300
- Aneuploidy involving non-disjunction in autosomes : This type of aneuploidy occurs due to trisomy of In any particular autosomal pair, having 3 instead of normal 2 chromosomes. Such persons may be
males 45 + XY = 47(2n + 1) or females 45 + XX =47(2n + 1). On the basis of the number of the autosome pair affected by trisomy, they can be of following types.
- Down’s syndrome : This autosomal abnormality is also known as Mongolian idiocy or mongolism. In Langdon Down of England (1866) studied the Mongolian idiocy and described the trisomic condition of their Down’s syndrome, a very common congenital abnormality arises due to the failure of separation of 21st pair of autosomes during meiosis. Thus an egg is produced with 24 chromosomes instead of 23. A Down’s syndrome has 3 autosomes in 21st pair instead of 2. Total number of chromosomes in this case is 2n + 1 (21st) = 47.
The affected children have a very broad fore head, short neck, flat palms without crease, stubby fingers, permanently open mouth, projecting lower jaw and a long thick extending tongue. They have low intelligence and are short heighted. They have defective heart and other organs. They are born to mothers aged 40 year and above during first pregnancy. They may survive upto 20 years under medical care.
They are called mongolian idiots because of their round, dull face and upper eyelids stretched downwards similar to mongolian race.
- Edward’s syndrome : This autosomal abnormality occurs due to trisomy of eighteenth pair of autosomes in which the number of chromosomes are 2n + 1 = 47. The child with this defect survives only about 6 Such children have defective nervous system, malformed ears and a receding chin.
- Patau’s syndrome : This is trisomy of thirteenth pair of autosomal This trisomic condition involves numerous malformations such as harelip, clefted palate and cerebral, ocular and cardiovascular defects. Such children usually survive for about 3 months only.
- Mutagens : Any substance or agent inducing mutation is called a mutagen. The mutagens may be broadly grouped into two
- Physical mutagens : It comprise mainly Radiation has been used to induce mutations for the first time by H.J. Muller (1927) on animals and L.J. Stadler (1928) on plants. Radiation that can produce mutation is known as effective radiations which are as follows.
- Ionizing (Particulate) : a-particles, b-rays, protons and
- Ionizing (non particulate) : X-rays, r-rays and cosmic
- Nonionizing : Ultraviolet rays
- Chemical mutagen : A large number of chemicals react with the four nucleotides and modify their base- pairing These are as follows.
- Base analogues : 5-bromodeoxyuridine (Brdu), 2-amino
(2) Chemicals modifying base-pairing
- Nitrous acid
- Alkylating agent : Nitrogen mustard, ethyl methane sulfonate (EMS), methyl methane sulfonate (MMS) and N-methyl-N’-nitro-nitroso-guanidine (NTG).
- Intercalating agents : Proflavin and acridine orange
- Genetic diseases in man : There are many diseases in man due to gene mutations. It is either dominant or recessive. The mutated person may become incapable to produce specified enzyme, so result in inborn errors of
(a) Chondrodystrophic dwarfism
- Chondrodystrophic dwarfism is a dominant autosomal mutation, most people are homozygous for recessive allele (c/c).
- The presence of one dominant C results in the premature closure of the growth areas of long bones of arms and legs, resulting in shortened and bowed arms and
(b) Huntington disease
- Huntington disease is caused by a dominant gene on chromosome 4.
- The mutated gene causes abnormality by producing a substance that interferes with normal metabolism in the brain that leads to progressive degeneration of brain
- The death comes ten to fifteen years after the onset of
- Also called “von Recklinghausen disease” caused by a dominant gene on chromosome 17.
- The affected individual may have ten spots on the skin which later may increase in size and
- Small benign tumours called neurofibromas may occur under the skin or in various
(d) Tay-Sachs disease
- Tay-Sachs disease results from the lack of the dominant gene on chromosome 15 for the production of hexosaminidase and subsequent storage of its substrate, a fatty substance known as glycosphingolipid, in
- The patient suffers from defective vision, muscular weakness and gradual loss of all mental and physical control, death occurs by the age of three or four
(e) Cystic fibrosis
- The most common lethal genetic disease due to a recessive mutation on the chromosome 7.
- The body produces abnormal glycoprotein which interferes with salt
- The mucus secreted by body becomes abnormally viscid and blocks passages in the lungs, liver and
(f) Alzheimer’s disease
- Alzheimer’s disease, named after the German neurologist Alzheimer, is a degenerative brain disease characterized by memory loss, confusion, restlessness, speech disturbances, erosion of personality, judgement, and inability to perform the functions of daily
- Alzheimer’s disease, a form of dementia, occurs in karyotypically normal
- About 5 percent of karyotypically normal individuals over age of 65 develop Alzheimer disease, and nearly 25 percent of those over age 80 do
- The brain of Alzheimer’s patients show a marked loss of
- These patients also show an accumulation of senile plaques, which are thickened nerve cell processes (axons and dendrites) surrounding a deposit of particular type of polypeptide called amyloid b protein.
- In the brain of normal persons, amyloid b protein is produced and processed in a number of ways from a large number of amyloid precursor
- The occurrence of Alzheimer’s disease in people with Down’s syndrome suggests that a gene or genes on chromosome 21 is
- Genetic mapping has demonstrated that the gene for amyloid b protein is located on chromosome 21; this gene encodes an Amyloid Precursor Protein (APP) that is enzymatically cleaved to produce amyloid b
- According to Bush (2003) Alzheimer’s disease is caused by a copper and zinc build up in the
(g) Marfan’s syndrome
- Marfan’s syndrome is due to dominant mutation resulting in the production of abnormal form of connective tissues and characteristic extreme looseness of joints.
- The long bones of body grow longer; fingers are very long called ‘spider fingers’ or arachnodactyly.
- The lenses in eyes become
- Albinism is an autosomal recessive mutation.
- An albino cannot synthesize melanin which provides black colouration to skin and hair.
- Albinism is due to tyrosinase deficiency.
- The enzyme tyrosinase normally converts the amino acid tyrosine to melanin through an intermediate product DOPA (dihydro phenyl alanine).
(i) Sickle-cell disease
- Sickle-cell disease is a genetic disease reported from negroes due to a molecular mutation of gene HbA on chromosome 11 which produces the b chain of adult
- The mutated gene HbS produces sickle-cell
- The sixth amino acid in b chain of normal haemoglobin is glutamic acid.
- In sickle-cell haemoglobin this amino acid is replaced by valine.
- The children homozygous (HbSHbS) produce rigid
- When oxygen level of the blood drops below certain level, RBCs undergo
- Such cells do not transport oxygen efficiently; they are removed by spleen causing severe anaemia.
- Individuals with the HbAHbA genotype are normal, those with the HbSHbS genotype have sickle-cell disease, and those with the HbAHbS genotypes have the sickle-cell
- Two individuals with sickle-cell trait can produce children with all three
- Individuals of sickle-cell trait are immune to malaria.
- Thalassemia is a human anaemia due to an autosomal mutant gene and when this gene is present in double dose, the disease is severe thalassemia major with death occurring in
- Heterozygous persons show a milder disease, thalassemia minor or also called Cooley’s anaemia.
- The persons suffering from thalassemia major are unable to produce b
- Their haemoglobin contains d chains like that of foetus which is unable to carry out normal oxygen transporting
- Alkaptonuria was the first of the recessive human trait discovered in 1902 by Archibald Garrod, ‘father of physiological genetics’ or ‘father of biochemical genetics’.
- Patients of alkaptonuria excrete large amounts of homogentistic acid in urine.
- Such urine turns black upon exposure to
- In normal person, homogentistic acid (alkapton) is oxidized by a liver enzyme homogentistic acid oxidase to maleyl acetoacetic
(l) Phenylketonuria (PKU)
- Phenylketonuria was discovered by the Norwegian physician Folling in 1934; an autosomal recessive mutation of gene on chromosome 12.
- PKU results when there is a deficiency of liver enzyme phenylalanine hydroxylase that converts phenylalanine into
- There is a high level phenylalanine in their blood and tissue
- Increased phenylalanine in the blood interferes with brain development; muscles and cartilages of the legs may be defective and the patients cannot walk
(m) Gaucher’s disease
- Gaucher’s disease is a genetic disease associated with abnormal fat metabolism, caused by the absence of the enzyme glucocerebrosidase required for proper processing of
- Non processing of lipids results in accumulation of fatty material in spleen, liver, bone marrow and
- The swelling of these organs occurs and patients usually die by the age of 15
- Galactosemia is inherited as an autosomal recessive, and the affected person is unable to convert galactose to
- Galactosemia is due to the deficiency of the enzyme Galactose Phosphate uridyl Transferase (GPT).
- Milk is toxic to galactosemic infants; child usually dies at three years of
(o) Taste blindness of PTC
- Taste blindness of PTC is a genetic trait, not a disease, discovered by Fox in
- PTC (phenyl thiocarbamide) is a compound of nitrogen, carbon and sulphur with sour taste.
- About 30% people lack the ability to taste PTC which is transmitted by a dominant gene
- The genotypes TT and Tt are tasters of PTC, while tt are non-tasters or taste blind
Fixing the sex of an individual as it begins life is called sex determination. The various genetically controlled sex-determination mechanisms have been classified into following categories
- Chromosomal theory of sex determination : The X-chromosome was first observed by German biologist, Henking in 1891 during the spermatogenesis in male bug and was described as X-body. The chromosome theory of sex determination was worked out by B. Wilson and Stevens (1902-1905). They named the X and Y chromosomes as sex-chromosomes or allosomes and other chromosomes of the cell as autosomes.
Sex chromosomes carry genes for sex. X-chromosomes carries female determining genes and Y-chromosomes has male determining genes. The number of X and Y chromosomes determines the female or male sex of the individual, Autosomes carry genes for the somatic characters. These do not have any relation with the sex.
- XX-XY type or Lygaeus type : This type of sex-determining mechanism was first studied in the milk weed bug, Lygaeus turcicus by Wilson and Stevens. Therefore, it is called Lygaeus These are two different patterns of sex determination in Lygaeus type.
- Female homogametic XX and male heterogametic XY : The homogametic sex (XX) is female and produces ova all of one type, e. having X-chromosome. The male is heterogametic-XY and produces sperm of two types. 50% of which possess X-chromosome and other 50% Y-chromosome. This is simple XX-XY type and is found in man, Drosophila and certain insects.
Example : In Drosophila total number of chromosomes is eight, of which six are autosomes, common to both male and female. The fourth pair is of sex chromosomes. In male this is represented by XY i.e. Karyotype of male Drosophila 6+XY and in female XX
i.e. 6+XX. Ova produced by female are all similar possessing 3+X chromosomes, whereas the sperm produced by male are 3+X and 3+Y in equal numbers.
- Female heterogametic and male homogametic : In fowl, other birds and some fishes, certain moths and butterflies, the female sex is heterogametic, with X and Y chromosome often represented by Z and W and laying two types of eggs, one half with X or Z chromosome and the other half with Y or W chromosome. The male sex is homogametic having XX or ZZ chromosomes. It produces sperm all of one
G XY E
G WZ E
- XX-XO type or Protenor type : Mc clung in male squash bug (Anasa) observed 10 pairs of chromosomes and an unpaired Their females have eleven pairs of chromosomes (22). Thus all the eggs carry a set of eleven chromosomes but the sperm are of the two types: fifty percent with eleven chromosomes and the other fifty percent with ten chromosomes. The accessory chromosome was X-chromosomes. Fertilization of an egg by a sperm carrying eleven chromosomes results in a female, while its fertilization by a sperm with ten chromosomes produces male. It is said to be evolved by the loss of Y-chromosome.
G XO E
- Haploid-diploid mechanism of sex determination : Hymenopterous insects, such as bees, wasps, saw flies, and ants, show a unique phenomenon in which an unfertilized egg develops into a male and a fertilized egg develops into a Therefore, the female is diploid (2N), and the male is haploid (N). eggs are formed by meiosis and sperms by mitosis. Fertilization restores the diploid number of chromosomes in the zygote which gives rise to the female. If the egg is not fertilized, it will still develop but into a male. Thus, the sex is determined by the number of chromosomes.
In honeybee, the quality of food determines whether a diploid larva will become a fertile queen or a sterile worker female. A larva fed on royal jelly, a secretion from the mouth of nursing workers, grows into a queen, whereas a larva fed on pollen and nectar grows into a worker bee. Thus, the environment determines fertility or sterility of the bee but it does not alter the genetically determined sex. The sex ratio of the offspring in the hive is controlled by the queen. She lays more fertilized eggs that produce worker females and fewer unfertilized eggs which produce haploid males. The queen mates only once in her life time, keeps a store of sperms in the seminal receptacle, and can control fertilization of eggs by releasing or not releasing sperms.
Male honey bee
Female honey bee
Female honey bee
Male honey bee
Fig : Haploid-diploid mechanism of sex determination in honeybee
Different types of chromosomal mechanisms of sex-determination in animals
|S. No.||Organisms||Heterogametic sex||Gamete||Zygotes|
|(1)||Drosophila, man etc.||Male||X and Y||All X||XX||XY|
|(2)||Protenor(Bug, Grasshopper)||Male||X and O||XX||XX||XO|
|(3)||Birds, moths||Female||All X||X and Y||XY||XX|
|(4)||Fumea (a moth)||Female||All X||X and O||X||XX|
- Quantitative or ratio theory of sex determination : B Bridges worked out ratio theory of sex determination in Drosophila. According to this theory the ratio of chromosomes to autosomes is the determining factor for the sex. Single dose of X-chromosome in a diploid organism produces male, whereas 2X-chromosomes produce a female. If a complete haploid set of autosomes is designated by A then 2A : X will give rise to male and 2A : 2X to female.
(a) Intersexes in Drosophila and ratio theory of sex determination : Bridges hypothesis was supported by studies of flies arising after abnormal distribution of chromosomes on account of non-disjunction. Due to abnormal meiosis during oogenesis both the X-chromosomes fail to separate and move to one pole of meiotic spindle. Thus few eggs are formed with single autosomal genome but with 2X chromosomes, i.e. (AXX) and other
with single autosomal genome but no sex chromosome (A). when such abnormal eggs are fertilized with normal sperm, the following result are obtained.
Results of fertilization of abnormal female gametes AAXXY – Female
AAXXX – Super female
AAX – Sterile male
AAY – Nonviable
Fig : Nondisjunction of X-chromosome in a female Drosophila leading to transfer of both X-chromosomes to one egg
Out of this progeny 1/4th males with no X are nonviable; the other 1/4 are without Y-chromosome and sterile. 1/4th females have an extra Y-chromosome while rest 1/4th females with 3X are super females. These are sterile with under developed sexual characteristics.
- Triploid intersexes and balance theory : The triploid flies with (3A + 3X) are much like the normal diploid females both in appearance as well as in fertility. On mating to diploid males their progeny consisted of following
- AAAXXX – Triploid females
- AAXX – Dilpoid females
- AAXXY – Diploid females
- AAAXX – Intersexes
- AAAXXY – Intersexes
- AAXY – Normal males
- AAXXX – Super females
- AAAXY – Super males
Fig : Results of a cross between triploid female and diploid male
The intersexes are sterile and intermediate between females and male, because the sex balance ratio in the intersexes comes to 2 : 3.
(2) Gyandromorphs in Dorsophila and ratio theory of sex determination : In Drosophila occasionally flies are obtained in which a part of the body exhibits female characters and the other part exhibits male characters. Such flies are known as gynandromorphs. These are formed due to misdivision of chromosomes and start as female with 2A+2X-chromosomes. One of the X-chromosomes is lost during the division of the cell with the result that one of the daughter cells possesses 2A+2X chromosomes and the other 2A+X. If this event happens during first zygotic division, two blastomeres with unequal number of X-chromosomes are formed. The blastomere with 2A+2X-chromosomes develops into female half, while the second blastomere with 2A+X chromosomes produces male half and the resultant fly is a bilateral gynandromorph. The occurrence of gynandromorphs clearly indicates that the number of X-chromosomes determines the sex of the individual.
Fig : Diagram to show origin of gynandromorphs
Fig : Gynandromorph of Drosophila in which right half is male and left half is female
- Genic balance theory : Based upon the observations of ratio theory Bridges put forward genic balance theory in which he suggested that every individual whether male or female possesses in its genotype genes for both male and female Which sex will actually develop is decided by the preponderance of that type of genes.
According to the genic balance theory of Bridges in Drosophila melanogaster, sex is determined by the ratio of the X-chromosomes and the set of autosomes. The Y-chromosomes play no part in sex determination it only governs male fertility. The XO flies are male, but sterile. Sex is governed by the ratio of the number of X chromosomes to sets of autosomes. The table given below indicates how the ratio of X/A help to determine the sex.
Ratio of X-chromosome to autosomes and the corresponding phenotype in Drosophila
|S. No.||Sex||Number of X-chromosomes||Number of autosomal set||Sex index X/A ratio|
|(1)||Super female||XXX (3)||AA (2)||3/2 = 1.5|
|Tetraploid||XXXX (4)||AAAA (4)||4/4 = 1.0|
|Triploid||XXX (3)||AAA (3)||3/3 = 1.0|
|2/2 = 1.0
1/1 = 1.0
|(3)||Intersex||XX (2)||AAA (3)||2/3 = 0.66|
|(4)||Normal male||X (1)||AA (2)||1/2 = 0.50|
|(5)||Super male||X (1)||AAA (3)||1/3 = 0.33|
Genes for maleness are carried on the autosomes, those for femaleness on the X-chromosomes. The sex index ratio of female is 1.0 while in males is 0.50. If X/A ratio is greater than 1.0 produces super females (meta females) and less than 0.50 produces super males. The X/A ratio lesser than 1.0 but greater than 0.5 (for example 0.66) result in intersexes. The degree of femaleness is greater where the X/A ratio is closer to 1.0 and the degree of maleness is greater where that ratio is closer to 0.5.
Human sex determination : The genic balance theory of sex determination is not universally accepted. Unlike Drosophila X : A does not influence sex determination. The key to sex determination in humans is the SRY (for sex region on the Y) gene located on the short arm of the Y-chromosome. In the male, the testis-determining factor (TDF) is produced by SRY on the Y-chromosome. TDF induces the medulla of the embryonic gonads to develop into testes. In the absence of SRY on Y, no TDF is produced. The lack of TDF allows the cortex of the embryonic gonads to develop into ovaries.
- Hormonal theory of sex determination : The sex determination theories of chromosomes and genic balance successfully apply to the lower animals but in higher vertebrates and under certain conditions in invertebrates, the embryo develops some characters of the opposite sex together with the characters of its own sex- It means, the sex changes under specific circumstances. This is due to the hormones secreted by the gonads of that animal.
(a) Free martinism : The influence of hormones on sex determination comes from free-martins often found in cattles. LILLIE and others found that where twins of opposite sex (one male and other female) are born, the male is normal but female is sterile with many male characteristics. Such sterile females are known as free martins.
The scientific explanation for the formation of free martins is the effect of hormones of the male sex on the female. In cattle the foetal membranes of the twins are
fused in such a manner that they have a common circulation of blood. The female hormone is produced at a slightly later stage in the development and guides its development towards female side. But since the twins have a common circulation and blood passes from one twin into the body of other twin, the male hormone which is produced slightly in advance of female hormone, enters the body of female twin and
before the female hormone onsets the development of
female characteristics it is already differentiated in the
guidance of male hormone. As a result the developing female is sterile.
Fig : Free martins in cattle
- Environmental theory of sex determination : In some animals, there is environmental determination of
- In Bonellia, a marine worm, the swimming larva has no sex. If it settles down alone, it develops into a large (2.5 cm) female. If it lands on or near an existing female proboscis, a chemical secreted from her proboscis causes the larva to develop into a tiny (1.3 mm) male. Male lives as a parasite in the uterus of the
- In turtles, a temperature below 28°C produces more males, above 33°C produces more females, and between 28°C to 33°C produces males and females in equal proportion, while in crocodile male sex is predominant at high temperature.
- Barr body in sex determination : Murray Barr (1949), a geneticist noticed a small body in the nucleus of the nerve cells of female cats which stained heavily with nuclear Further investigations showed that not only nerve cells, but many other cells from female cats only, had these bodies, now known as sex chromatin or Barr
bodies. It was soon learnt that such bodies can be found in females of many mammals including human. In women the Barr body lies against the nuclear membrane like a round disc in the neutrophil blood cells, skin cells, nerve cells, cells of mucous membrane, cells of lining in vagina and urethra. They are absent in man. These bodies are thus named after the discover Barr.
Barr bodies are used to determine the sex of unborn human embryos. In this technique called amniocentesis sample of the amniotic fluid is examined for Barr bodies. The sex is determined by the presence or absence of Barr bodies in epithelial cells of embryo present in the amniotic fluid sample. Studies from the cells of aborted embryos show that Barr bodies can be
(N – 1 = 0) 46, XX
(N – 1 = 1)
distinguished at about 15 or 16th day after conception that means
(N – 1 = 2) 48, XXXX (N – 1 = 3)
several weeks before the formation of gonads. Whereas sex of embryo is determined soon after fertilization, sex differentiation can be noticed in third week stage of pregnancy.
Fig : Chromosome variations and Barr body
Mary Lyon hypothesis : According to the British geneticist Mary Lyon (1961), one of the two X- chromosomes of a normal female becomes heterochromatic and appears as Barr body. This inactivation of one of the two X-chromosomes of a normal female is the dosage compensation or Lyon’s hypothesis.
It is estimated that number of Barr bodies is one less from the total number of X chromosomes present in embryo. Therefore, Barr bodies are also used to decide the genic constitution of such persons who have irregular number of sex chromosomes. More than one X chromosome in such persons is transformed into Barr bodies.
|S. No.||Individual||No. of X chromosome||No. of Barr body (X – 1)|
|(1)||Normal woman||XX||2–1 = 1 (one barr body)|
|(2)||Women with Turner’s syndrome||XO||1–1 = 0 (no barr body)|
|(3)||Super female||XXX||3–1 = 2 (two barr bodies)|
|(4)||Man||XY||1–1 = 0 (no barr body)|
|(5)||Man with Klinefelter’s syndrome||XXY||2–1 = 1 (one barr body)|
Sex can also be distinguished by studies of simple blood smears. The neutrophils, the most common of the white blood corpuscles, have a nucleus divided into two or three lobes. Female neutrophils showing a small drumstick extending out from one of the nuclear lobes, is a definite indication of the female chromosome component in the cells.
- Goldschmidt brought forward the quantitative theory of .
- The term “gynandromorphism” was introduce by Goldschmidt in
- Drumstick is the sex chromatin present in the neutrophil (Polymorphonuclear leucocyte) of 3 to 5% cells in females, but not in
- Y chromatin (Y body) can be identified as bright spot by staining cells with acridine
- First X-linked gene was discovered by H. Morgan (1910) for white eye mutation.
- Pedigree of colour blindness was first described by Horner (1876).
- It is also called bleeder’s disease, first studied by John Cotto in
- Duchenne Muscular Dystrophy (DMD) is the disease which is characterized by a progressive weakness and loss of
- Inheritance of beard in a man is sex-limited.
- In melandrium (Garden flower) the sex determination type is XX-XY.
Sex chromosomes of some animals and man besides having genes for sex character also possess gene for non sexual (somatic) characters. These genes for non sexual characters being linked with sex chromosomes are carried with them from one generation to the other. Such non-sexual (somatic) characters linked with sex chromosomes are called sex linked characters or traits, genes for such characters are called sex linked genes and the inheritance of such characters is called sex linked inheritance. The concept of sex-linked inheritance was introduced by THOMAS
- MORGAN in 1910, while working on Drosophila melanogaster.
The sex chromosomes in man and Drosophila are almost same in structure. The X and Y chromosomes, although different (non-homologous) in shape, size and structure, have atleast some similar (homologous) part which is known as homologous segment and the remaining part as non-homologous or differential segment. Genes for sex linked characters occur in both segments of X and Y chromosomes. Many sex linked characters (About 120) are found in man. Such characters are mostly
Red eyed E
White eyed G
(i) Types of sex linked inheritance
(a) Diandric sex linked or X linked traits
: Genes for these characters are located on non- homologous segment of X chromosome. Alleles of
these genes do not occur on Y chromosome. Genes
Gametes R r
of such characters are transferred from father to his daughter and from his daughter to her sons in F2 generation. This is known as Cris-cross inheritance.
As the genes for most sex linked characters are
X X Y
F1 Generation R r R
X X X Y
located in X chromosome, they are called X-linked
Red eyed E
Red eyed G
characters e.g. colour blindness and haemophilia in man and eye colour in Drosophila.
R Ova r
- Sex linked inheritance in Drosophila : Drosophila melanogaster has XX and XY sex chromosomes in the female and male Its
eye colour is sex linked.
X X X Y
R R r R R rF Generation
X X X X X Y X Y
Allele of the eye colour gene is located in the X
Red eyed Red eyed Females
Red eyed White eyed Males
chromosome, and there is no corresponding allele
in the Y chromosome. The male expresses a sex-
Fig : Sex-linked inheritance in Drosophila melanogaster. Note the
transmission of sex chromosomes carrying eye colour gene R and r in a cross between red-eyed female and white-eyed male
linked recessive trait even if it has a single gene for it, whereas the female expresses such a trait only if it has two genes for it. The normal eye colour is red and is dominant over the mutant white eye colour. The following crosses illustrate the inheritance of X-linked eye colour in Drosophila.
- Red-eyed female ´ White-eyed male : If a homozygous red-eyed female fly is mated with a hemizygous (having a single allele for a trait) white-eyed male fly, all the F1 flies, irrespective of their sex, are red When the red-eyed male and female flies of F1 are intercrossed (equivalent to self pollination in peas), the F2 flies are in the ratio of 2 red-eyed females to 1 red-eyed male to 1 white-eyed male. Thus, the red-eyed and white- eyed flies are in the ratio of 3 : 1 in F2 generation (Mendelian monohybrid ratio).
If XR represents a gene for red eye and Xr that for white eye colour, the above cross may be diagramed as follows. The above cross shows that a recessive X-linked trait follows criss-cross inheritance, i.e., transmission from the father to the grandsons through the daughters. The latter are called carriers because they have a trait but do not express it.
- Sex linked inheritance in man. Colour blindness and Haemophila are the two main sex linked or X-linked disease are found in man.
- Colour blindness : Person unable to distinguish certain colours are called colour blind. Several types of colour blindness are known but the most common one is ‘red-green colour blindness’. It has been described by HORNER (1876).
The red blindness is called protanopia and the green blindness deutoranopia. X-chromosome possesses a normal gene which control the formation of colour sensitive cells in the retina. Its recessive allele fails to do its job properly and results in colour blindness. These alleles are present in X chromosome is evidenced by the following results.
- If a normal female is married to a colour blind
Results : All her sons and daughter have normal colour vision, but all daughters are carrier.
- But when her daughter (carrier) are married to man with normal colour vision
Result : Some colour blind sons are formed.
Conclusion : It means that a woman with normal colour vision whose father is colour blind gives birth to children, of which about half of the sons are colour blind and other half are normal.
- If a colour blind woman is married to a normal
colour- blind male
Result : All her sons are colour blind whereas all the daughter have normal colour vision.
- But when these daughters having normal colour vision (Heterozygous) are married to colour blind man.
colour blind female
colour blind male
Result : The colourblind grandsons and grand daughters are produced with almost equal number of normal grandsons and grand daughters.
Conclusion : It means that a colour blind woman has sons all colour blind and daughters all with normal vision and a colour blind woman always has a colour blind father and her mother is a carrier.
Inheritance of colourblindness
The above results could easily be explained with the assumption that colour vision is sex linked character and its gene is present on X-chromosome, Y-chromosome lacks its allele. Always male receives its X-chromosome from mother (through ovum) and Y-chromosome from father (through sperm), whereas the female receives one X- chromosome from each parent (through ovum and sperm). From the above result following conclusions may be drawn.
- Colour blindness is more common in males than in females.
- Two recessive genes are needed for the expression of colour blindness in female, whereas only one gene gains expression in
- Males are never
- Colour blind women always have colour blind fathers and always produce colour blind
- Colourblind women produce colour blind daughters only when their husbands are colour
- Women with normal colour vision, whose fathers are colour blind, produce normal and colour blind sons in approximately equal
- Haemophilia : In haemophilia the blood fails to clot when exposed to air and even a small skin injury results in continuous bleeding and can lead to death from loss of
It is also called bleeder’s disease, first studied by John Cotto in 1803. The most famous pedigree of haemophilia was discovered by Haldane in the royal families of Europe. The pedigree started from Queen Victoria in the last century. In a patient of haemophilia blood is deficient due to lack necessary substrate, thromboplastin. It is of two types.
- Haemophilia-A : Characterized by lack of antihaemophilic globulin (Factor VIII). About four-fifths of the cases of haemophilia are of this
- Haemophilia-B : ‘Christmas disease’ (after the family in which it was first described in detail) results from a defect in Plasma Thromboplastic Component (PTC or Factor IX).
Like colour blindness, haemophilia is a well known disorder which is sex-linked recessive condition. The recessive X-linked gene for haemophilia shows characteristic Criss-cross inheritance like the gene for colour blindness. Its single gene in man results in disease haemophilia, whereas a woman needs two such genes for the same.
- Defective enamel : It is a dominant X-linked trait and is inherited through a dominant X-linked As X-chromosome is present in both man and woman, it is expressed in both the sexes. However, such persons have defective enamel on teeth like grey or brown unlike pure white enamel in a normal man.
Another example of dominant X-linked gene is the dimpled cheeks. Dimple may occur on one or both the cheeks.
- Holandric or Y-linked traits : Genes for these characters are located on non-homologous segment of Y chromosome. Alleles of these genes do not occur on X Such characters are inherited straight from father to son or male to male e.g. hypertrichosis of ears in man.
- Hypertrichosis of ears : This is a condition in which excessive amount of large hair grow on the pinna in man. It is sex- linked trait controlled by a gene present on the non-homologous segment of the Y-chromosome. Hence its inheritrance is called holandric inheritance and it appears only in It passes
directly from father to son. Fig : ‘Hairy ears’, an inheritance by holandric gene
- XY-linked inheritance : The genes which occur in homologous sections of X and Y-chromosomes are called XY-linked genes and they have inheritance like the autosomal
Example of XY-linked genes are those of the inheritance of following
- Xeroderma pigmentosa, a skin disease characterized by the pigment patches and cancerous growth on the
- Nephritis, a kidney
- Sex-influenced traits : The autosomal traits in which the dominant expression depends on the sex hormones of the individual are called sex-influenced These traits differ from the sex limited traits which are expressed in only one sex. It has following examples.
- Baldness in man : Baldness in humans is the best example of sex-influenced traits. This trait is due to a single mutant gene but the expression of the heterozygous is different in man and woman. This is a hereditary character controlled by sex-influenced gene which is dominant in men and recessive in The difference in expressions may be caused by varying amounts of male and female sex hormones. If autosome dominant gene ‘B’ is regarded to inherit the baldness, the homozygous (BB) dominant condition will cause baldness in man as well as women. This gene for baldness acts recessively in woman when present in heterozygous (Bb) condition, the baldness develops in males only because under such condition the phenotype expression (baldness) is influenced by androgen hormone secreted by man. A heterozygous female is normal. A homozygous recessive condition (bb) does not allow baldness to develop either in male or female.
Phenotypic expression of genotype for baldness
The different phenotypes in men and women shown in above table are sex-influenced characters and also called sex-controlled traits.
The progeny that would be obtained from the marriage of heterozygous (B/b) man and woman for baldness have been shown below.
Progeny resulting from the marriage of bald men and non-bald women both heterozygous
- Length of index finger : It is another example of sex-influenced trait in man. It is controlled by a gene which is dominant in male and recessive in the female. When the hand is placed on white board the tip of the fourth finger or ring finger just touches a horizontal line, it is seen that index or second finger does not reach this line in many cases. In some persons index finger extends beyond this horizontal line as shown in figure. The short index finger is inherited as a dominant trait in men and as a recessive condition in
Fig : Sex influenced inheritance of length of index finger
- Sex limited traits : Traits or characters which develop only in one sex are called sex-limited They are produced and controlled by the genes which may be located on autosomes in only one sex. Such genes are responsible for secondary sexual characters as well as primary sexual characters. They are inherited according to Mendel’s laws.
Sex-limited traits in man : Beard is produced by sex-limited genes in man, which does not develop in woman. Breast development is normally limited to woman. In case of abnormalities of hormonal secretions facial hair may develop in woman and a faminine breast development may occur in man. It means that expression of sex- limited characteristics in vertebrates depend upon the secretion of sex hormones. For example genes for deep masculine voice, masculine body, masculature in man will express themselves only in the presence of male hormone. Genes for faminine voice and faminine musculature on the other hand express themselves in the absence of male hormone and will not require the secretion of female hormone. Similarly, breast development in woman requires the presence of female hormone rather than mere absence of the male hormone. It can be concluded that certain sex-limited characteristics are expressed in the absence of certain hormones and other express only in the presence of sex-hormones.
Inheritance of hundreds of characteristics such as polydactyly, haemophilia, colour blindness, attached ear lobes and tongue rolling, generation after generation in particular families of man have been studied. In order to conduct such study, a standard method has been used to represent the family pedigree in a concise, easily understood form so that one can visualize the entire pedigree (family history) at a glance of the chart.
(i) Pedigree chart and symbols : It is customary to represent men by squares and women by circles in a chart for study of pedigree analysis. Marriage is indicated by a connecting horizontal line and the children by attachment to a vertical line extending downward from the horizontal line. Individuals having particular characters to be studied are denoted by solid squares or circles while those not having them are indicated by outlines only. Twins are denoted by bifurcating vertical lines.
Fig : Commonly used symbols in pedigree chart
In such a pedigree analysis a person who is the beginner of the family history is called proband. It is called propositus, if male and poposita, if female. The children of such parents are known as sibs or siblings. So a family is constituted by such parents and their siblings. Sometimes, a very large family is formed as a result of interconnected marriages. Such a circle of large persons interconnected is called Kindred.
In order to study pedigree analysis we have taken some of the important case histories as follows :
- Polydactyly : The pedigree of this trait has become standard usage among the geneticists and it helps us to understand the process of transmission of this
This inheritable trait was discovered when a woman brought her young
daughter to a doctor for examination as she had an extra finger on one hand and an extra toe on one foot. On investigation it was found that child’s father had this characters (though his extra finger had been removed
surgically) and that her brother also had the character. The other two children of this family had normal number of fingers and toes. This type of inheritance is typical of characters which are known as dominant.
- Attached ear lobes : This is a recessive type of inheritance and is
inherited in a different way.
Fig : Pedigree of polydactyly
- Two parents with free ear lobes produced two children with attached ear lobe in a family of five
Free ear lobes
Fig : Pedigree of free ear lobes
- In another family both parents had attached ear lobes but all the four of their children had this trait of attached ear
Attached ear lobes
Fig : Pedigree of attached ear lobes
- Tongue rolling : Some persons are capable of rolling their tongue while others are not gifted with this A couple both of whom are tongue roller have two out of these children as tongue rollers.
Can not roll tongue
Fig : Pedigree of tongue rolling
- Crooked little fingers : This is a family pedigree of a human family where crooked little fingers are inherited through a simple dominant gene. In this pedigree a woman had two sons one of which had crooked little Her husband also had same type of defective fingers. On further survey of her husbands, family it was found that her husband’s sister and mother both had crooked little fingers, as well as his grandfather also possesses this trait. The characteristic also appeared in more distant relatives.
Fig : Inheritance of crooked little fingers (dominant trait)
Twins : Two birth occurring at the same time in human are called twins, they are of peculiar genetic interest. The hereditary basis of a number of human traits has been established by the study of twins. There are 3 kinds of twins.
- Identical or monozygotic twins : Identical twins are formed when one sperm fertilizes one egg to form a single zygote. As a result of separation of two daughter cells or blastomeres after the first cleavage, each of the cell develops into a separate individua Such individuals are called identical twins. Since they develop from a single zygote, they are called monozygotic twins. They have the same genotype and phenotype and are of same sex. Differences if any, may be due to different environmental conditions.
- Siamese twins or conjoint twins : Like monozygotic twins, siamese twins also originate from one zygote but the daughter cells formed as a result of first cleavage fail to separate completely and they remain joined at some They grow into two individuals joined together. Thus the two individuals called conjoint twins remain attached at one or more parts of the body. They were first studied in the country Siam, hence called Siamese twins. Siamese twins usually do not survive after birth although a few cases of their survival are well known. They are always of the same sex, same genotype and phenotype.
- Fraternal twins : They are dizygotic twins formed from the two eggs fertilized by two sperms separately but at the same time. They may be both males, both females or one male and one female. They may have different genotypic constitution and different Thus fraternal twins develop in same environment with different constitution but are the members of same age. They resemble each other just like any two brothers and sisters. Although they may be of same sex but due to different hereditary traits, they may carry congenital variations.
Among the twins fraternal twins are most common and Siamese twins are most rare.
Two zygotes or fertilized eggs
Each zygote develops separately into
a boy or a girl
Two cells separate and
devlop into two boys or two girls
Two cells do not separate and develop into
Two united individuals
Fig : Human twins : formation and types
Eugenics, Euthenics and Euphenics.
- Eugenics : The term eugenics (Gr. Eugenes, well born) was coined by British scientist Sir Francis Galton in Galton is called ‘Father of eugenics’ as this branch has been started by him.
Eugenics is the branch of science which deals with improvement of human race genetically. This aspect of human betterment aims to improve the human germplasm by encouraging the inheritance of best characteristics so that defective characters may be eliminated. Eugenics attempts to attain its objective bilaterally by suggesting a number of ‘do’s and ‘don’ts’ to improve the human gene pool. The ‘don’ts’ are meant to check inheritance of the poor or undesirable germplasm, while the do’s aim at perpetuating desirable germplasm to be inherited. By this method aim of improvement of human race may be achieved by two ways :
- Positive eugenics : In this approach of eugenics the future generations are improved by encouraging the inheritance of better Following methods may be adopted to achieve this.
- Planned marriages : The selection of mate for marriage should be made on the basis of better traits rather than on the basis of dowry, caste or religion will give rise to the progeny with better traits.
- Perevention of loss of good germplasm : Many intelligent, specialists, educationists and politicians with better traits should be encouraged getting marriage at early stage and practice polygamy may contribute for more and more utilization of good
- Medical engineering : To destroy the unwanted germplasm or such genes before their expression
Liederberg (1963) put forth a novel idea of medical engineering.
- Germinal choice or eutelegenesis : In human beings artificial fertilization or insemination is a biological Muller (1963) put forward the idea of production of children of high mental qualities and good traits by artificial fertilization of a woman of high quality traits with the sperms of desired best man.
- Genetic counselling : Production of healthy progeny should be the endeavour of man to ensure a better future for Genetic counselling can make a significant contribution in this direction. It can provide much needed relief for families with history of genetic diseases. Genetic counselling is even useful after marriage. A Rh– woman with Rh+ partner when aware of the implications in the second child, can go for suitable medical aid well in advance.
- Negative eugenics : This is a negative aspect of improving mankind by restricting the transmission of poor and defective This restriction can be brought about in the following ways.
- Segregation : Persons with serious abnormal hereditary defects like feeble mindedness, epilepsy, leucoderma, criminals, immorals and stupid people, should be isolated e. should not be permitted to mingle and marry with normal, intelligent persons.
- Restriction on blood marriages : Marriage between close relative like cousins tend to bring together the recessive alleles in homozygous condition and can be expressed in haemophilia, albinism and colour
- Sterilization : The most effective method to stop the persons with defective germplasm to produce offsprings is the sterilization. This prevents the transmission of undesirable traits in man and woman by vasectomy and tubectomy
- Euthenics : Euthenics is the improvement of human race by improving the environmental conditions, e., by subjecting them to better nutrition better unpolluted ecological conditions, better education and sufficient amount of medical facilities.
- Better education : Education is one of the surest agents which can provide better humanity. The conditions of surroundings e. the immediate environment of an individual has a great bearing upon personality of the person. The society which an individual chooses determines to some extent, his character. Medical facilities are largely responsible for maintenance of sound health. Employment conditions determine the degree of fulfillment of the individual’s basic requirements and hence it influences his entire outlook. Euthenics attempts to provide the best of education, the healthiest of surroundings, the finest of societies, full medical facilities and rewarding employment conditions.
- Subsidization of superior students : Euthenics requires that a best student be selected and be provided opportunities for his multifaceted Students of no definite class and group may be equally intelligent. A few are most intelligent, some are average, still others are below average and some are dull or feeble minded or idiots. A definite scale to measure the mental ability has been prescribed which is known as intelligence quotient.
Intelligence quotient (IQ) : The ratio between actual (chronological) age and mental age multiplied with 100 is known as I.Q. Intelligence quotient is the mental competence in relation to chronological age in man. It can be denoted by following formula.
I.Q. = Mental age ´ 100 Actual age
By applying this formula we can easily calculate the IQ, such as if a 10 year child has mental age 14, his IQ will be
I.Q. = 14 ´ 100 = 140
On the basis of different levels of I.Q. persons are classified as follows.
|(1)||0 – 24||Idiot|
|(2)||25 – 49||Imbecile|
|(3)||50 – 69||Moron|
|(4)||70 – 79||Dull|
|(5)||80 – 89||Ordinary|
|(6)||90 – 109||Average|
|(7)||110 – 119||Superior|
|(8)||120 – 139||Most superior|
|(9)||140 or more||Genius|
- Euphenics : The study of born defectives and their treatment is called The term euphenics was given by A.C. Pai (1974) for symptomatic treatment of human genetic disease especially in born errors of metabolism. Following methods can be employed as euphenic measures.
- Amniocentesis : It is a test to detect genetic diseases as well as the sex of embryo during development in mother’s womb. Amniotic fluid is tested and if embryo has genetic disease the embryo can be
- Infusion of missing enzyme : Genetic physiological diseases occur due to lack of particular enzymes. Infusion of such missing enzyme may help in treatment of such
- Genetic engineering : Treatment of the gene controlling genetic disease by genetic surgery and genetic engineering is also helpful in