L8-Sex linkage PDF

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Genes& I nheritance

Lecture 8: Sex linkage Genetics

Genes& I nheritance F irst Big Question : W hy are there more genetic diseases in males?

Genetics

Sex chromosomes • One sex hemizygous (eg. human males X, Y) • Distinguishes sexes • Affects sex ratios

Genetics

Sex ratios

Genetics

Sex chromosomes • One sex hemizygous (eg. human males X, Y) • Distinguishes sexes • Affects sex ratios • Affects linkage ratios

Genetics

Sex linkage Ratios of crosses are not as expected. F1 example: Red (W+) dominant to white (W) so for W+W+ x WW would expect F1 to be 100% red (W+W). However, get 3 red: 1 white. Genetics

Sex linkage Ratios of crosses are not the same in both sexes. F1 example: Red (W+) dominant to white (W) so for W+/W+ x W/W would expect F1 to be 100% red (W+/W). However, get 100% red females and 50% red: 50% white males. Genetics

Sex linkage Ratios of crosses are not as expected. F2 example: Red (W+) dominant to white (W) so for W+W x W+W would expect F2 to be 3 red: 1 white. However, get 5/8 red: 3/8 white. Genetics

Sex linkage Ratios of crosses are not the same in both sexes. F2 example: Red (W+) dominant to white (W) so for W+/W+ x W/W would expect F2 to be 3 red: 1 white. However, get 3 red: 1 white females and 1 red: 1 white males.

Genetics

Sex-linkage: nomenclature • Sex-linkage refers to genes located on sex chromosomes • X-linkage refers to genes located on a specific sex chromosome, the X-chromosome • In order to indicate that a gene is on a sex chromosome, a special nomenclature is used (eg XAXa and Xa Y). Otherwise, it is assumed that the gene is autosomal. Genetics

X-linkage: H umans

Genetics

X-linkage: H umans X-linkage affects ratios in pedigrees as well. Example: higher frequency of males with X-linked recessive genetic disorders than females.

Genetics

Sex linkage: H umans X-chromosome linkage – Hemophilia – Colour blindness – Muscular dystrophy – Fragile X – thousands more

Y-chromosome linkage – H-Y antigen – Hairy ears? Genetics

Genes& I nheritance F irst Big Question : W hy are there more genetic diseases in males? Because males only have one X-chromosome! Genetics

Genes& I nheritance Second Big Question: D o we need to know the mode of inheritance ? D o we need to know if genes are autosomal or sex linked? Genetics

M ode of I nheritance Why need to know the mode of inheritance? 1. Required to predict progeny phenotypic outcomes from crosses or pedigrees 2. Required to manipulate progeny phenotypic outcomes 3. Required to determine the genotype of individuals 4. Required to determine which traits are linked 5. Required for selection of traits Genetics

Genes& I nheritance Second Big Question: So we do need to know if genes are autosomal or sex linked! But how do we determine the mode of inheritance? Genetics

M ode of I nheritance How do we determine the mode of inheritance? 1.Look at the data and make an educated guess to develop an hypothesis for the mode of inheritance 2.Test hypothesis (eg chi square test) 3.If not accepted, then develop a new hypothesis and/ or perform experimental crosses for more data

Genetics

M ode of I nheritance How do we determine the mode of inheritance from a pedigree? 1.Look at the pedigree and decide the mode of inheritance. Try the simplest model first. Is the trait dominant or recessive ? 2.Then look at the pedigree and decide if the trait is autosomal or sex-linked. 3.Can ask questions OR can try models to see if they fit. Genetics

M ode of I nheritance: Pedigrees YES

DOMINANT

Do affected progeny always have at least one affected parent? NO RECESSIVE

Genetics

M ode of I nheritance: Pedigrees Do affected progeny YES always have at least one affected NO parent?

Do affected males have DOMINANT affected sons AND daughters? RECESSIVE

YES

AUTOSOMAL

SEX-LINKED (X-linked)

NO – daughters only

Genetics

M ode of I nheritance: Pedigrees Do affected progeny YES always have at least one affected parent? NO

DOMINANT

Do affected males have affected sons AND daughters?

RECESSIVE Are both

YES

AUTOSOMAL

NO

SEX-LINKED

YES

AUTOSOMAL

sexes affected? SEX-LINKED NO – sons mostly Genetics

M ode of I nheritance: Pedigrees Do affected progeny YES always have at least one affected NO parent?

Do affected YES males have affected DOMINANT sons AND daughters? NO YES RECESSIVE Are both sexes affected? NO

AUTOSOMAL

SEX-LINKED (X-LINKED) AUTOSOMAL

Do affected YES SEX-LINKED males have affected NO sons?

Y-LINKED

X-LINKED

Genetics

M ode of I nheritance: Pedigrees Let’s try some pedigrees for practice…. Bring out some writing implements…

Genetics

M ode of I nheritance: Pedigrees Do affected progeny YES always have at least one affected NO parent?

Do affected YES males have affected DOMINANT sons AND daughters? NO YES RECESSIVE Are both sexes affected? NO

AUTOSOMAL

SEX-LINKED (X-LINKED) AUTOSOMAL Do affected YES SEX-LINKED males have affected NO sons?

Y-LINKED

X-LINKED

Genetics

M ode of I nheritance

How do we make an educated guess regarding the mode of inheritance? 1.Start with simplest model • Dominance (eg complete, partial, co-, no) • Autosomal versus sex linked 2.Other considerations • Lethal alleles, multiple alleles • Multiple genes (ie, epistasis) • Environment (esp. qualitative vs quantitative) Genetics

Sex linkage: Questions How is sex linkage observed? – Reciprocal crosses – Unexpected female: male phenotypic ratios in pedigrees

How can sex linkage be proved? – Statistically test for expected Mendelian ratios given sex linkage (eg chi square) Genetics

Genes& I nheritance Third Big Question: H ow do men cope with a more or less useless Y-chromosome?

Genetics

Sex chromosomes: pairing at metaphase

Genetics

X-chromosome crossovers

Genetics

X-Y recombination

Genetics

Sex chromosomes • One sex hemizygous (eg. human males X, Y) • Distinguishes sexes • Affects sex ratios • Affects linkage ratios • Affects gene expression

Genetics

X-inactivation How do female animals cope with having 2 X-chromosomes? How do male animals cope with having only 1 X-chromosome? Is there a mechanism of dosage compensation?

Yes!!! X-inactivation

Genetics

X-inactivation

Genetics

X-inactivation STEPS: A. Xist RNA is transcribed on one X-chromosome B. Xist RNA coats Xchromosome C. X-chromosome is inactivated by DNA methylation and less acetylation of histones because of Xist RNA presence Genetics

X-inactivation

• Inactivated X-chromosome is heterochromatic (highly condensed) in cell during entire the cell cycle and in subsequent daughter cells. • Called a Barr body and is an example of epigenetics. Genetics

X-inactivation

• Random which X-chromosome (maternal or paternal) is inactivated, except marsupials (paternal only). So eutherian females are mosaic. • However, if one X-chromosome is defective, then all cells may have the same X-chromosome inactive. Genetics

X-inactivation Example of mosaicism in cats: Calico coat colour in females. Males either orange or black. (White from autosomal gene.)

Genetics

X-inactivation Example of mosaicism in humans: ectodermal dysplasia

Genetics

X chromosome: D osage compensation X-inactivation is only one type of dosage compensation. There are other mechanisms, including increased gene expression (eg. flies).

Genetics

X-chromosome: D osage compensation Example: dosage compensation in flies

Genetics

Genes& I nheritance Third Big Question: H ow do men cope with a more or less useless Y-chromosome? They just need one “good” X-chromosome! But how is sex determined then? Genetics

Sex chromosomes • One sex hemizygous (eg. human males X, Y) • Distinguishes sexes • Affects sex ratios • Affects linkage ratios • Affects gene expression • Sex determination Genetics

Sex determination in plants

Includes sex chromosomes, sex genes, hormones Genetics

Sex determination: birds

Genetics

Sex determination in bees

Genetics

Sex determination: eutherian mammals

Genetics

Sex determination: mammals

Genetics

Sex determination: comparison

Genetics

Genes& I nheritance Third Big Question: H ow do men cope with a more or less useless Y-chromosome? They just need SRY gene and one “good” X-chromosome! Genetics

Genes& I nheritance End of lecture 8 Everything you didn’t want to know about sex Genetics...