The X chromosome and triple repeat disorders

Question 1

What is the SRY?

Answer 1

Sex determining region o the Y chromosome

Question 2

What is the default sex?

Answer 2

female - xx

Question 3

At what point do the gonads differentiate?

Answer 3

7 weeks

Question 4

What is PAR and what does it do?

Answer 4

Pseudoautosomal regions
Gene content present on both X and Y
Helps chromosomes align in meiosis

Question 5

Klinefelter’s syndrome

Answer 5

47 XXY

Men are affected - they appear taller than average, small testes, gynaecomastia, infertile

Question 6

Turner’s syndrome

Answer 6

X
Females affected - short stature, shield chest, infertility
Mosaic form

Question 7

Mosaicism

Answer 7

Different cells have different chromosome numbers - in Turner’s some have 45 and some have 46

Question 8

X inactivation

Answer 8

One X in females is silenced by chromatin

Question 9

Autosomal dominant inheritance

Answer 9

• 50% risk in offspring
• M and F equally affected
• Affected individuals have affected parent
• Occurs in every generation

Question 10

Autosomal recessive inheritance

Answer 10

• 25% risk in offspring
• Parents are carriers
• M and F equally affected

Question 11

X-linked recessive inheritance

Answer 11

• Mother or father carries defective gene
• Males will pass on Y chromosome to sons - no M-M transmission but predominantly affects males
• Girls get faulty gene from father
• Mother can pass faulty X on to sons
• E.g. haemophilia A and B and Duchenne’s muscular dystrophy

Question 12

X-linked dominant inheritance

Answer 12

• No M-M transmission
• F>M affected but M more severely affected
• Rett Syndrome (delayed development from 1yo)
• Rett Syndrome normally kills males so there are more living female patients
• Fragile X syndrome - developmental delay in childhood
• Fragile X caused by trinucleotide repeat disorder

Question 13

trinucleotide repeat disorders

Answer 13

• Fragile X: X chromosomes have fragile site. FMR1 is on X chromosome long arm - gene has region of repeats of CGG
• Methyl added to CGG sequence inactivates gene - absence of protein causes fragile X
• TRDs are unstable during meiosis, can be mediated by DNA, mRNA or protein and show anticipation (increased clinical severity and earlier age of onset in successive generations)
• > 200 copies is fragile X

Question 14

What is anticipation?

Answer 14

In a hereditary disease, you get symptoms earlier and more severely as the generations go on