Heredity (L. hereditas – heirship or inheritance) is the transmission of characters from parents to offspring. Inheritance is the process by which characters or traits pass from one generation to the next. Variation is the degree of differences in the progeny and between the progeny and the parents. The branch of biology that deals with the study of heredity and variations is known as Genetics (Gk. genesis – descent; Bateson, 1906). GENETIC TERMINOLOGY
(i) (ii) (iii) (iv) (v)
Hemizygous : It is a condition where a gene is present in only a single copy in a diploid cell. Hemizygous condition occurs for those genes which are found on differential parts of XY chromosomes . Non - Alleles : They are factors present on different gene loci . F1 generation : It is also called first filial generation . The term was coined by Bateson (1905). F2 generation : It is second filial generation which is formed through selfing or inbreeding of individuals of F1 generation . The term was coined by Bateson (1905) . Pure Line : It is a strain of true breeding individuals which are genetically pure or homozygous because they have been formed either through repeated self fertilization of ancestors or breeding between identical homozygous ancestors Monohybrid Ratio : It is a ratio found in F2 generation of a monohybrid cross where F1 individuals are selfed . Monohybrid ratio is of two types (i) phenotypic Monohybrid Ratio . 3:1 (ii) Genotypic Monohybrid Ratio 1:2:1 . Dihybrid Ratio : It is the ratio found in F2 generation of a dihybrid cross where F1 individuals are selfed. Dihybrid ratio is of two types (i) phenotypic Dihybrid Ratio 9:3:3:1 . Here first and last are similar to parental types while the middle ones are recombinants . (ii) Genotypic Dihybrid Ratio . 1 : 2 : 2 : 4 : 1 : 2 : 1 : 2 : 1 The first and last are genotypically parental type , the rest are recombinants of various types. Punnet Squares : It is a checker board or square divided into smaller acquires where all the possible types of gametes are shown , male in horizontal row and female in vertical column . Mendel’s Calculations : Mendel used algebraic formulae and theory of probability for his calculations . Example , gametes carrying two different factors when allowed to randomly fuse , produce three types of individuals by the formula (A+a)2 = AA + 2Aa + aa Similarly , the probability of any of the two alternate 1 events is 50% or . The probability of joint occurrence of two different events is multiple of their 2 1 ⎛1 1⎞ individuals probabilities, i.e. 25% or ⎜ × ⎟ . 4 ⎝2 2⎠ Back Cross : The cross between one of the two parents, homozygous dominant or homozygous recessive with F1 individual is termed as back cross. Where as the cross between specific individual and homozygous recessive parent is termed as test cross. Where F1 individuals is back crossed with the parent possessing dominant phenotype, no recessive, individuals are obtained. But when F1 progeny is back crossed with its recessive parent, both dominant and recessive phenotype appear in the progeny. Again back cross can be used for obtaining pure line breeds. F1 hybrid double dominant
Tt gametes T t TT 50% Ratio = 1 : 1 T Tt TT T Tt 50%
Back cross TT offsprings
Test Cross : Test cross is the mating of an incompletely known genotype to a genotype which is homozygous recessive at all loci under consideration. Test cross is the most specific and short method to ensure the genotype of an individual showing dominant characteristic for a particular trait. F1 hybrid double recessive
Tt gametes T Tt t Tt 50% t tt tt t tt 50%
Monohybrid Test Cross Ratio – 1 : 1 Dihybrid Test Cross Ratio – 1 : 1 : 1 : 1
Trihybrid Cross. After analyzing dihybrid crosses, Mendel also conducted some trihybrid or three- factor crosses. The results of such crosses analyzed by applying the principles of segregation and independent assortment.
INCOMPLETE DOMINANCE (1 : 2 : 1) When the dominant allele does not mask completely the phenotypic expression of the recessive allele. This results in the blending of phenotypic expression. The alleles maintain their individuality and segregate from each other of during gametogenesis. The F2 progeny produced exhibit the phenotypic & genotypic ratio of 1: 2 :1. Exp : When a homozygous red flowered is crossed with a homozygous white flowered pea plant. The F1 heterozygotes are found to have pink flowers. When F1 hybrid are breed amongs themselves the F2 generation have identical phenotype & genotypic, ratio of 1 Red (RR) : 2 pink (Rr) : 1 white (rr)
Red Parents. RR X White rr
F1 Parents R Rr r X R Rr r
RR Red 1 Rr : Rr Pink 2 : rr White 1
(Similar results have been reported in snapdragon and four ‘O’ clock plant too)
Amongest Animals : The incomplete dominance is well examplified in Andalusian fowls. In Andalusian fowls, the black colour of the feathers has been found to dominant incompletely over the splashed white colour of the feathers. When a black feathered flown is crossed with a white feathered fowl, the F1 hybrids have blue feathers. The blue feathered F1 heteroygotes produces a F2 progeny in the phenotypic & genotypic ratio of 1 : 2 : 1 as illustrated below.
F1 Parents. Bb X Bb
Black feathered BB X B B
White feathered. bb
Gametes B b B b
BB Bb Blue 2 Bb bb White splashed 1 F2
Codominance (1 : 2 : 1) : In the phenomenon of codominance, dominant and recessive alleles lack typical dominant and recessive relationships. In the heterozygous condition, both the alleles of the genes are capable of expressing themselves & therefore in the heterozygotes the traits occur side by side. The F2 progeny produce the phenotypic & genotypic ratio of 1 : 2 : 1. Exp. In cattle. in one breed of cattle genotype Iw produces white coat colour. IR genotype expresses as red coat colour. When a white coat colour of cattle is crossed with Red coat coloured cattle, the F1 hybrids have a roan coat colour. Which is not an intermediate between red & white but has a mixture of red hair & white hairs. White Red
Iw Iw Iw
IR IR IR
F1Parent I I F1Gametes I
I I Roan
w I I
w I I
I I Red
Incomplete Dominance versus Codominance. In the incomlplete dominance, the heterozygote has a phenotype that is intermediate between the phenotypes of the homozygotes. In codominance, the position is somewhat different. Here, both the genes are expressed independently in the heterozygote, rather than producing an intermedate producing an intermediate phenotype. The human alleles IAIB produce the blood group AB in which the erythrocytes have on their plasma membrane both antigen A and antigen intermediate between A and B. LETHALITY (LETHAL GENES) The term ‘lethal’ is applied to those changes in the genome of an organisms that produces effect severe enough to cause death. The fully dominant lethal allele kills the carrier individual both in its homozygous & heterozygous condition. The individual with dominant lethal allele is die before they can produce the progeny. The recessives lethal allele kills the carrier individuals only in the homozygous condition. The lethal allele modify the 3 : 1 phenotypoic ratio into 2 : 1. (a) Lethal alleles in Plants (2 : 1) : In snapdragon 3 types of plants occur. (i) Green plants (due to presence of chlorophyll). (ii) Yellowish green plants (due to presence of carotenoids) (iii) White Plants (due to absence of chlorophyll) Homozygous green plants have genotype CC & cc are white plants without chlorophyll. The yellowish green plant also called golden or auria plants have the genotype Cc. when two auria plant are crossed Albino plant dies as it lack chlorophyll. The ratio is modified into 2 : 1, the homozygous recessive genotype being lethal. Similar lethal genes controlling the amount of chlorophyll is found in zea mays. The recessive allele (g) controls the chlorophyll content and exhibits its effect in homozygous and heterozygous condition (gg) combination is lethal and so the ratio is modified into 2 : 1] (b) Lethal genes in Animals : (yellow lethals in mice) In mice, an incompletely dominant allele ‘Y’ for yellow coat has been found lethal in homozygous condition. This condition of yellow lethal of mice first reported by Cue ‘not (1905). yy genotype produces black coat colour in mice. When homozygous black mouse was crossed with another black mouse only black mice were produced. Cue´not then crossed a black homozygous mouse (yy) with a yellow mouse (Yy) we get a ratio of 1:1 by him, proving that yellow mouse was heterozygous. When a yellow mouse was crossed with another yellow mouse, cue´not found that the yellow & black mice appeared in the ratio of 2 : 1. (c) Lethal genes in man 1. Congenital ichthyosis It is an example of homozygous recessive lethal gene in man. Children afflicted with this disease are born, with crusted leathery skin with deep fissures. These fissures lead to bleeding infection and death. 2. Amaurotic idiocy It is caused by a recessive homozygous gene. Bearer of this genotype are affected in Juvenile stage itself. They lose their eye sight between 4 & 7 years of age. This is accompanied by mental degeneration & finally death before adolescence. 3. Sickle Cell anemia : In certain Africa tribe, the presence of codominant gene. Hb1S in homozygous condition (codominant with HbA.) causes a disease called sick cell anemia, which lead to death.
In the presence of Hb1S, Hb1S, the haemoglobin formed not being the right type (the haemoglobin found in sickle called individual has valine, instead of glutamic acids) as one of its 287 amino acids) lead to sickle shaped RBC instead of the normal biconcave oval appearance. This is turn affects the oxygen carrying capacity of haemoglobin, & impedes blood circulation as well. However, the heterozygous individuals Hb1S, Hb1A, manifest none of these symptoms & are outwardly indistinguishable from the normal homozygous (Hb1A, Hb1A). 4. Huntington’s chorea : It is caused due to a dominant gene. Huntington’s chorea leads to degeneration of cerebral cortex, corpus striatum especially the caudate muscles. The onset of this disease is in the middle age marked by : Occurrence of rapid, jerky, ceaseless involutionary movements. Poor memory, irritability & violence. The gene responsible for this disease lie on chromosome 4 and finally causes death of the individuals.
MUTIPLE ALLELES The genetic systems described so for have been limited to a single pair of alleles. The maximum number of alleles at a gene locus that any individual possess is 2, with 1 on each of the homologous chromosomes. But since, a gene can be changed to alternative, forms by the process of mutation, a large number of alleles is theoretically possible in a population of individual. This is because the nucleic acid structure of a gene consists of many nucleotides & variations can arise at each of the nucleotide positions along its length. Thus are more than only two possible kinds of alleles in a gene, hundreds or perhaps thousands of possibilities exists and called multiple allelic series i.e A1, A2, A3...................An. A capital letter is used to designate the allele that is dominant to all others in the series. The corresponding small letter designates the allele that it recessive to all others in the series. Other alleles, intermediate in their degree of dominance between these two extremes, are usually assigned the small, letter with some suitable super script. (i) Example The colour of Drosophila eyes is governed by a series of alleles that cause the hue to vary from red or wild type (WT or W) through coral (WCO), blood (Wbl) eosin (we), cherry (Wch), apricot (Wa), honey (wh), buff (wbf) tingeed (Wt), pearl (wP) & ivory (wi) to white (w). Each allele in the system except w can be considered to produce pigment, but successively less is produced by alleles as we proceed down the hierarchy : wt > wCo > wbl > we > wch > wa > wh > wbf > wt > wp > wi > w. The wild type allele (wt) is completely dominant & w is completely recessive to all other allele in the series : Example of multiple alleles is found in the ABO blood group system of humans, where the allele IA for the A antigen is codominant with the allele IB for the B antigen. Both IA & IB are completely dominant to the allele i, which fails to specify any detectable antigenic structure. The hierarchy of dominance relationship is symbolized as (IA = IB) > i (I stands for isohemagglutinogen).
Thus when paired with either IA or IB, its effect is masked. Since three alleles of the gene exists in a population, it is considered a multiple allele system. The genotypes that produce the four blood groups are represented in the following table. Genotype Blood type ii O A A A I I ;I i A B B B I I ;I i B A B I I AB If the blood groups of the parents are known, the blood groups of the children can be determined (or vice versa) by using the Punnett- square method. Possible combinations of allele that are associated with ABO blood type. COLLABORATOR FACTOR (9 : 3 : 3 : 1 RATIO) In collaboration two different genes which are present on separate loci interact to produce some totally new single trait phenotype that neither of the genes by itself could produce. Example : It is illustrated by the inheritance of combs in poultry. Two genes control the development of comb. Gene R gives rise to rose comb and P produces pea comb. Both pea and rose comb are dominant over single comb. When genes for rose and pea comb are together they interact to form walnut comb. If chicken with rose and pea comb are crossed the F1 individuals have walnut comb and in F2 generation walnut, rose, pea and single comb individuals are produced in the ratio of 9 : 3 : 3 : 1. SEX - LINKED INHERITANCE The term sex linkage or sex linked inheritance was used to describe the association of a hereditary trait with sex because the gene was in a sex chromosome. Most sex-linked genes are found in the Xchromosome. Haemophilia & colour blindness are sex linked traits in man. Haemophilia : Haemophilia or bleeder’s disease is a sex-linked disease in which a slight cut results in profuse bleeding. This disease is restricted entirely to men. They cannot transmit this disease to their sons However, they can transmit the disease to their grandsons through their daughters. The genes of this disease were found to be recessive and are contained in the X-chromosome Y-chromosome carries no genes for this trait. Let the gene for normal clotting be represented by XH and its recessive allele by Xh which is responsible for haemophilia.
Different types of genotypes theoretically possible for male and female, are as follows :
– (i) XHY – Normal (ii) XhY - haemophilic – (i) XHXH – Normal (ii) XHXh – carrier (non haemophilic)
(iii) Xh Xh – haemophilic. The progeny of a marriage between a haemophilic man (XhY) and a normal woman (XHXH) is given below. Thus, all the sons will be normal as they receive the dominant gene (XH) from the mother and a Y chromosome from the father which contains no gene for this trait. All the daughters will have the genotype XHXh. Such daughter, though normal are carriers of the disease and they can pass on the trait to half of her sons even when she marries a normal man. The progeny of a marriage between a carrier woman (XHXh) and a haemophilic man (XhY) will be as follows : Colour blindness : A vision defect, refers to the inability to distinguish between red and green colours. The genes controlling this characters are present in the X chromosome Y chromosome does not bear any gene for this character. The gene for normal vision is dominant over its allele for the defect. A colour blind man has only one gene for the defect while a colour blind women has two the heterozygous female looks normal but actually carries a gene for the defect which it can transmit to her offspring of such a female is called a carrier.
BASIS OF SEX DETERMINATION
Drosophila and human chromosome complements consist of autosomes (2A) and sex chromosomes ; female with 2A +XX and male with 2A + XY . In humans and Drosophila , the male produces two types of gametes while the female produces only one type of gamete . Y chromosome carries a gene cry (sex determining region) which codes for a product called testis - determining factor (TDF) . TDF is required for the development of male sex and its absence leads to the development of female sex. Sex is determined by a pair of chromosomes or sex chromosomes and Y is responsible for maleness in both the species . Evidence gathered from study of variations in sex chromosome composition in these cases and subsequent molecular genetic analysis proved that Y does determine maleness in humans and other mammals , but not in Drosophila .Calvin Bridges on Drosophila demonstrated that in this fly , sex determining factor is the ratio of number of X chromosomes to the sets of autosomes . Thus 2A + 2X or 3A + 3X having an X/A ratio of 1.0 are female and fertile. (3X +2A or X/A ratio 1.5) metafemales are produced which are weak and infertile . 2A +XY and 2A+XO are males , though the latter are sterile . Thus, an X/Y ratio of 0.5 is required for male sex differentiation. When the ratio decreases , e.g 3A +XY with X/A ratio = 0.33 , infertile metafamales are produced . Bridges also showed that flies with X/A ratio between 0.5 and 1.0 exhibited a lot of morphological and sexual abnormalities . These results suggested that in Drosophila male development factors are localised on autosomes instead of sex chromosomes . The X - chromosome determining genes such as Sxl . Such a mode of sex differentiation is referred to as the genic balance theory of sex determination . Birds and butterflies , males are XX and females are XY . To avoid confusion , these forms are usually expressed as ZZ (male ) and ZW (female ). Female produces two types of gametes . Thus , the egg determines the sex of the offspring.
HUMAN GENETICS We, like all other living organisms , also follow the principles of inheritance . One of the biggest difficulty encountered is that controlled crosses cannot be made in human inheritance studies . Also the number of offspring produced per mating is very restricted unlike many other organisms such as pea plant.
Pedigree analysis is carried out for studying inheritance of human traits because the common Mendelian experiments cannot be carried out over human beings due to the following reasons . (i) Generation period is long in human beings (20 - 25 years). (ii) In many cases human traits are influenced by a number of factors . (iii) A scientific worker can study human inheritance for not more than two to three generations . (iv) Progeny of a couple is small. A family tree or pedigree is drawn for families having genetically transmitted diseases or traits. This is constructed based on information gathered about all members of the family over many generations. This pedigree is represented with certain standard symbols. For carrying out simple Mendelian analysis involving recessive or dominant allele, certain cluses or simple rules are sought from the pedigree. In the case of recessive allele, for example, characteristic condition can appear in the progeny of apparently unaffected parents. Moreover, two affected individuals cannot have unaffected child. Quite often, such recessive alleles are revealed by close marriages, such as cousin marriages. Simple pedigree analyses have extensive use not only in medical research but also in the day-to-day counselling of prospective parents who would like to be guided about the possibilities of transmitting a dieased condition to their children.