5 Sex Linked Disorders Flashcards
What is male hemizygosity?
Males will expressa all the genes on the X-chromosome
What is x-chromosome inactivation?
As only one X chromosome is needed (as evidence by males), the inactivation event is a “dosage” compensation reducing expressin to one allele. Leads to a variety of presentation in females
The X and the Y chromosomes are homologs. They pair at meiosis. This is mediated by?
Pseudoautosomal regions
What are pseudoautosmal regions?
Both the X and the Y chromosomes have regions, at the telomeres that functions like any other chromosome. Genes in the is region need biallelic expression, crossing over (PAR regions) occurs between the genes in this region
How does x-chromosome inactivation happen?
Typically it is random from cell to cell wich X-chromosome is inactivated. So in general 50% of the cells in the female body will have one X activated and the other 50% with have the opposite activated
What is a barr body in a cell?
It is the x chromosome in a female that is inactivated
How many barr bodies does a female with Turner syndrome have?
0, Barr bodies = number of X chromosomes - 1
What happens if there is a mutant gene on the X-chromosome?
This can result in variable phenotype and disease expression in females. X-linked recessive diseases are usually more severe in males but can be expressed in females to varying degrees
Why is the Y chromosome important?
Necessary for male development, testicular development governed by the SRY, the sex-determining region on the Y, absence of SRY produces female phenotype, presence produces male, spermatogenesis governed by Yq genes
What is the pattern of inheritance for sex-linked genetic disorders?
All are X-linked, usually recessive. Mutated Y-chromosme genes produce infertility so are not inherited
In what sex are X-linked dominant disorders more prevelant?
X-linked dominant disorders are more prevelant in females than males (often lethal to males and pregnancies are lost. Only one affected gene needed to produce clinical efffects.
In what sex are X-linked recessive disorders more prevelant?
Almost exclusively seen in males, female carriers have milder symptoms, rare for a female to bea homozygote
What is hemophilia A?
X-linked recessive, reduced factor VII, excess bleeding, amount of factor VII activity determines clinical severity
What is duchenne muscular dystrophy?
DMD is X-linked recessive. Normal at birth, progressive muscle weakness, wheelchair age 10, progression to death, pseudohypertrophy, respiratory insufficiency
What are the genetics behind DMD?
DMD gene on Xp21 encodes a protein called dystrophin, mutations are primarily deletions, 1/3 of cases are new mutations, rest have a female carrier mother, carrier women clinically asymptomatic (may have elevated creatine kinase levels)
