Coupling and repulsion human genetics

B.Sc. Cell biology and genetics Paper, Notes for B.Sc Biotechnology students, Coupling and repulsion human genetics, includes examples

1. Linkage and Crossing Over & Human Genetics By Dr. Krishna Assistant Professor in Biotechnology Tumakuru

2. Linkage and Crossing Over: A chromosome possesses many genes & all genes present in the chromosome are inherited together. Mendel’s Second Law, or the law of the independent assortment, is valid for genes located in different chromosomes. These genes segregate independently during meiosis. However, Mendel’s Second Law is not valid for phenotypical features conditioned by genes located in the same chromosome (genes under linkage), since these genes, known as linked genes, do not separate during meiosis (except for the phenomenon of crossing over). The fruit fly, or drosophila, is suitable for studying genetics because it presents many distinct traits but only has four chromosomes (one sex chromosome and three autosomes).  Linkage : Study of inheritance of all genes present in a chromosome together. All genes in a chromosome are together referred as linked genes & they form a linkage group . The total number of linkage group in an organism is equal to its  haploid number of chromosomes .

3. Bateson & Punnet: While working on sweet pea ( Lathyrus odoratus ) observed that genes for flower color & pollen shape remain together and do not assort independently according to Mendel’s law of Independent assortment. Test cross failed to produce 1:1:1:1 ratio & instead produced 7:1:1:7. They gave the Coupling & Repulsion theory : Coupling: when genes come from the same parent they enter the same gamete & are inherited together. Repulsion: genes are inherited separately when genes come from different parents  & they enter different gametes

4. T H Morgan’s Linkage: He worked on Drosophila . Linked genes show 2 types of arrangement: Cis arrangement : dominant alleles of 2 or more genes are present in one chromosome & its recessive alleles in its homologue.  AB/ab . This is Coupling. Trans arrangement:  the dominant allele of one pair & recessive of the other pair together lie in a chromosome. Ab/ aB . This is Repulsion. Linked genes are of 2 types : Complete linkage : genes for 2 or more characters appear together for two or more generations in their parental combination. They are closely located in the chromosome. Incomplete linkage:  the parental combination of 2 or more characters are not retained in the next generations. They are not closely located in the chromosome. Linked genes are genes present on the same chromosome. Linked genes are inherited together. Genes are linearly arranged in a chromosome. Strength of linkage: Genes which are closely located show strong linkage & genes which are located far show weak linkage. He stated that Coupling & Repulsion are two aspects of Linkage .

5. Crossing over: It is the  exchange of segments between non-sister chromatids of homologous chromosomes. It occurs during pachytene stage of prophase I in meiosis. Crossing over always occurs between linked genes. It produces recombination of linked genes which play very important role in evolution . Recombination frequency helps in finding out the distance between genes.   Given by Sturtevant. Recombination frequency helps in the  construction of genetic maps of the chromosomes.

6. In a dihybrid cross: When the test cross result is 1:1, genes are linked and there is no crossing over. If the test cross result is 1:1:1:1 means the genes are independently assorting (present on separate chromosomes). If in the test cross result parental combination is more than 50% & recombination is less than 50% , the genes are linked and crossing over has occurred.

7. Coupling and Repulsion Hypothesis of Gene. Bateson and Punnett in 1906, described a cross in sweat pea, where failure of gene pairs to assort independently was exhibited. Plants of a sweat pea variety having blue flower (BB) and long pollen (LL) were crossed with those of ano­ther variety having red flower (bb) and round pollen (II). F 1 individuals ( BbLl ) had blue flower and long pollen.

8. Linkage in Maize: Maize provides a good example of linkage. Hutchinson crossed a variety of maize having coloured and full seed (CCSS) with a variety having colourless and shrunken seeds ( ccss ) . The gene C for colour is dominant over its colourless allele c and the gene S for full seed is dominant over its shrunken allele s. All the F 1 plants produced coloured and full seed. But in a test cross, when such F 1 females (heterozygous) are cross pollinated with the pollen from a plant having colourless and shrunken seeds (double recessive), four types of seeds are produced (Fig. 5.8). From the above stated result it is clear that the parental combinations are more numerous (96.4%) than the new combination (3.6%). This clearly indicates that the parental characters are linked together. Their genes are located in the same chromosome and only in 3.6% individuals these genes are separated by crossing over. This is an example of incomplete linkage.

9. Linkage In Drosophila Morgan (1911) crossed an ordinary wild type Drosophila with grey body and long wings (BB VV) with another Drosophila (mutant type) with black body and vestigial wings ( bbvv ). All the hybrids in F 1 generation are with grey bodies and long wings ( BbVv ) i.e., phenotypically like the wild type of parents. If now a male of F, generation (Bb Vv ) is back crossed with a double recessive female (test cross) having black body and vestigial wings ( bbvv ) only parental combinations are formed in F 2 generation without the appearance of any new combinations. The results indicate that grey body character is inherited together with long wings. It implies that these genes are linked together. Similarly, black body character is associated with vestigial wing. Since only parental combinations of character appear in the offspring of F 2 generation and no new or non-parental combinations appear, this shows complete linkage. Complete linkage is seen in Drosophila males.

10. Types of Linkage: Depending upon the presence or absence of new combinations or non-parental combinations, linkage can be of two types: ( i ) Complete Linkage: If two or more characters are inherited together and consistently appear in two or more generations in their original or parental combinations, it is called complete linkage. These genes do not produce non-parental combinations. Genes showing complete linkage are closely located in the same chromosome. Genes for grey body and long wings in male Drosophila show complete linkage. (ii) Incomplete Linkage: Incomplete linkage is exhibited by those genes which produce some percentage of non-parental combinations. Such genes are located distantly on the chromosome. It is due to accidental or occasional breakage of chromosomal segments during crossing over.

11. Significance of Linkage: ( i ) Linkage plays an important role in determining the nature of scope of hybridization and selection programmes. (ii) Linkage reduces the chance of recombination of genes and thus helps to hold parental characteristics together. It thus helps organism to maintain its parental, racial and other characters. For this reason plant and animal breeders find it difficult to combine various characters.

12. Human Genetics Autosome: Allosome : Autosomes differ from allosomes because autosomes appear in pairs whose members have the same form but differ from other pairs in a diploid cell, whereas members of an allosome pair may differ from one another and thereby determine sex. Human genetics is the study of inheritance as it occurs in human beings . Human genetics encompasses a variety of overlapping fields including: classical genetics , cytogenetics , molecular genetics , biochemical genetics , genomics , population genetics , developmental genetics , clinical genetics , and genetic counseling .

13. Autosomal dominant inheritance Autosomal traits are associated with a single gene on an autosome (non-sex chromosome)—they are called " dominant " because a single copy—inherited from either parent—is enough to cause this trait to appear. This often means that one of the parents must also have the same trait, unless it has arisen due to an unlikely new mutation. Examples of autosomal dominant traits and disorders are Huntington's disease and achondroplasia . Autosomal recessive inheritance Autosomal recessive traits is one pattern of inheritance for a trait, disease, or disorder to be passed on through families. For a recessive trait or disease to be displayed two copies of the trait or disorder needs to be presented. The trait or gene will be located on a non-sex chromosome. Because it takes two copies of a trait to display a trait, many people can unknowingly be carriers of a disease. From an evolutionary perspective, a recessive disease or trait can remain hidden for several generations before displaying the phenotype. Examples of autosomal recessive disorders are albinism , cystic fibrosis .

14. X-linked and Y-linked inheritance X-linked genes are found on the sex X chromosome. X-linked genes just like autosomal genes have both dominant and recessive types. Recessive X-linked disorders are rarely seen in females and usually only affect males. This is because males inherit their X chromosome and all X-linked genes will be inherited from the maternal side. Fathers only pass on their Y chromosome to their sons, so no X-linked traits will be inherited from father to son. Men cannot be carriers for recessive X linked traits, as they only have one X chromosome, so any X linked trait inherited from the mother will show up Females express X-linked disorders when they are homozygous for the disorder and become carriers when they are heterozygous. X-linked dominant inheritance will show the same phenotype as a heterozygote and homozygote. Just like X-linked inheritance, there will be a lack of male-to-male inheritance, which makes it distinguishable from autosomal traits. One example of an X-linked trait is Coffin–Lowry syndrome , which is caused by a mutation in ribosomal protein gene. This mutation results in skeletal, craniofacial abnormalities, mental retardation, and short stature. X chromosomes in females undergo a process known as X inactivation . X inactivation is when one of the two X chromosomes in females is almost completely inactivated. It is important that this process occurs otherwise a woman would produce twice the amount of normal X chromosome proteins. The mechanism for X inactivation will occur during the embryonic stage. For people with disorders like trisomy X , where the genotype has three X chromosomes, X-inactivation will inactivate all X chromosomes until there is only one X chromosome active. Males with Klinefelter syndrome , who have an extra X chromosome, will also undergo X inactivation to have only one completely active X chromosome. Y-linked inheritance occurs when a gene, trait, or disorder is transferred through the Y chromosome. Since Y chromosomes can only be found in males, Y linked traits are only passed on from father to son. The testis determining factor , which is located on the Y chromosome, determines the maleness of individuals. Besides the maleness inherited in the Y-chromosome there are no other found Y-linked characteristics.

15. Pedigrees analysis A pedigree is a diagram showing the ancestral relationships and transmission of genetic traits over several generations in a family. Square symbols are almost always used to represent males, whilst circles are used for females. Pedigrees are used to help detect many different genetic diseases. A pedigree can also be used to help determine the chances for a parent to produce an offspring with a specific trait.

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