21, 22. X inactivation and inheritance related to sex Flashcards
What does a reciprocal cross do?
To determine if the trait is on the X chromosome. The crosses have different outcomes for sex linked
What are some examples f X linked traits in humans?
- Colour blindness
- Haemophilia
- Duchenne muscular dystrophy
- Fragile X
What is Haemophilia A?
Deficiency of factor VIII
- Severe impairment of clotting
What is Haemophilia B?
Christmas diseae, deficiency of Factor IX
- Mild impairment of clotting
What causes the fragile X mutation?
- Expansion in a CGG repeat in the FMR gene (Fragile X mental retardation protein). Where affected have >200 repeats
What does the FMRP protein do?
It is a regulatory protein which funcitons in neurons and dendrites. The expansion results in no protein because it disrupts transcription and translation
What happens in X inactivation?
In early embryonic development of a female, one X is switched off. In human it is randomly either the maternal or paternal X
What happened to the cell lines after one X is inactivated>
Once an X is inactivated all cell lines derived from this line have the same X inactivated
what is the inactive X chromosome known as?
The barr body which is made of heterochromatin
What is mosaicism?
- When female is heterozygous for an X linked recessive mutation
- Some cells will express normal copy and others will have mutated X switched on
When does X inactivation occur during development?
After several cell divisions of the zygote (blastocyst stage)
Does x inactivation occur in oocyte?
It is reversed in the female germline so all ova have an active X
What are the steps for X inactivation?
- The Xist gene is one the X chromsome
- Transcription of the Xist gene makes an interference RNA
- The RNA binds to the X chromosome from which it was transcribed
- Methylation and histone deacytelation attract chromsomal proteins that form heterochromatin, inactivating the chromosome
Are all genes on the X inactivated?
Not all genes
- Some loci escape inactivation
- Mainly pseudoautosomal region where inactivation occurs
What is atypical lyonisation/manifesting heterozygote?
- Heterozygous females may show symptoms of an X linked recessive trait
- If switching ff by chance means more Xs with mutant allele left on than Xs with normal allele
What is a sex influenced trait?
Expression in either sex is less extreme
- Example: balding seen in males more
- B1 appears dominant in males and recessive in females
What causes the baldness mutation?
Baldness mutation leads to over expression of 5 alpha reductase which stimulates dihydrotestosterone which binds to receptors in the scalp. Over expression leads to hair falling out
What are some symptoms of Polycystic Ovary Disease?
- Abnormal, irregular periods
- Acne, decreased breast size, weight gain
- Development of male sex characteristics
- Diabetes
How are PCOD and MPB related?
- MPB is also associated in families with PCOD in females
- PCOD and MPB are due to alleles of the same gene
- Different thresholds for phenotypic expression in females and males
What are sex limited traits?
Where the phenotype is limited to one sex by can be passed to offspring by either sex
What is precocious puberty?
- Example of sex limited trait where boys have an early onset of puberty between 2-5 years
- Both parent can pass it on but only males express it
