21, 22. X inactivation and inheritance related to sex

Question 1

What does a reciprocal cross do?

Answer 1

To determine if the trait is on the X chromosome. The crosses have different outcomes for sex linked

Question 2

What are some examples f X linked traits in humans?

Answer 2

• Colour blindness
• Haemophilia
• Duchenne muscular dystrophy
• Fragile X

Question 3

What is Haemophilia A?

Answer 3

Deficiency of factor VIII

- Severe impairment of clotting

Question 4

What is Haemophilia B?

Answer 4

Christmas diseae, deficiency of Factor IX

- Mild impairment of clotting

Question 5

What causes the fragile X mutation?

Answer 5

• Expansion in a CGG repeat in the FMR gene (Fragile X mental retardation protein). Where affected have >200 repeats

Question 6

What does the FMRP protein do?

Answer 6

It is a regulatory protein which funcitons in neurons and dendrites. The expansion results in no protein because it disrupts transcription and translation

Question 7

What happens in X inactivation?

Answer 7

In early embryonic development of a female, one X is switched off. In human it is randomly either the maternal or paternal X

Question 8

What happened to the cell lines after one X is inactivated>

Answer 8

Once an X is inactivated all cell lines derived from this line have the same X inactivated

Question 9

what is the inactive X chromosome known as?

Answer 9

The barr body which is made of heterochromatin

Question 10

What is mosaicism?

Answer 10

• When female is heterozygous for an X linked recessive mutation
• Some cells will express normal copy and others will have mutated X switched on

Question 11

When does X inactivation occur during development?

Answer 11

After several cell divisions of the zygote (blastocyst stage)

Question 12

Does x inactivation occur in oocyte?

Answer 12

It is reversed in the female germline so all ova have an active X

Question 13

What are the steps for X inactivation?

Answer 13

1. The Xist gene is one the X chromsome
2. Transcription of the Xist gene makes an interference RNA
3. The RNA binds to the X chromosome from which it was transcribed
4. Methylation and histone deacytelation attract chromsomal proteins that form heterochromatin, inactivating the chromosome

Question 14

Are all genes on the X inactivated?

Answer 14

Not all genes

• Some loci escape inactivation
• Mainly pseudoautosomal region where inactivation occurs

Question 15

What is atypical lyonisation/manifesting heterozygote?

Answer 15

• 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

Question 16

What is a sex influenced trait?

Answer 16

Expression in either sex is less extreme

• Example: balding seen in males more
• B1 appears dominant in males and recessive in females

Question 17

What causes the baldness mutation?

Answer 17

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

Question 18

What are some symptoms of Polycystic Ovary Disease?

Answer 18

• Abnormal, irregular periods
• Acne, decreased breast size, weight gain
• Development of male sex characteristics
• Diabetes

Question 19

How are PCOD and MPB related?

Answer 19

• 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

Question 20

What are sex limited traits?

Answer 20

Where the phenotype is limited to one sex by can be passed to offspring by either sex

Question 21

What is precocious puberty?

Answer 21

• 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