GEN (Mastick):X-linked

Question 1

fruquency of affected male vs frequency of carrier femaile

Answer 1

1q.

2q

Question 2

Haldane Principle

Answer 2

In pop with stable disease frequency,

rate of spontaneous new mutation = rate loss of alleles

Question 3

In Duchene muscular dystrophy, what’s the rate of spontaneous new alleles?

Answer 3

1/3 sooo high

Question 4

“Variable but may be high”?

Answer 4

say that when we don’t know the carrier status of the proband male’s mother, and there are no other cases of the disease in the family tree

Question 5

scenario: 1/3 mutations of duchenne are spontaneous; there is 1/3500 pop risk of duchenne; proband male is due to spontaneous mutation. what is the recurrence risk in males and then in females?

Answer 5

Males; 1/3500 times a third.
Female: 1/3500 times third.
so 1/10500

Question 6

In “variable but could be high” cases, who do we test first?

Answer 6

we test the proband (usually a male proband) coz then it’s just so much easier to find the mutation AND THEN know exactly what to look for later on.

Question 7

1/3rd of reproductive lethal mutations are spontaneous. true or false?

Answer 7

truuuuueeee.

Question 8

What proportion of x chromosomes gets inactivated in barr bodies?

Answer 8

one X chromosome in each somatic cell in females is inactivated randomly

Question 9

how are x chromosomes inactivated?

Answer 9

DNA methylation by, XIST RNA, dna/CONDENSATION.

Question 10

If extra x chromosomes, which ones will get condensed into barr bodies?

Answer 10

all but one

Question 11

Inactivation

Answer 11

occurs by DNA methylation, XIST, RNA and DNA condensation

Question 12

When does inactivation occur in developement?

Answer 12

at IMPLANTATION (1002 of cells), and then it is fixed; subsequent daughter cells will have the same X chromosome (AKA CLONAL PROPAGATION). This results in MOSIACISM.

Question 13

Does X inactivation of a chromosome completely shut down every gene on that chromosome?

Answer 13

For the most part, yes, but just a few cells, so that’w why turner’s syndrome isn’t too severe. FOR THE MOST PART, dosage compensation is not needed.

Question 14

X-chromosome inactivation ratio

Answer 14

1/2 express genes on maternal X; 1/2 express on paternal X.

Question 15

At the blastocyte, what cells express the placenta/etraembryonic structures?

Answer 15

the maternal X; that’s why the maternal X is so important in development.

Question 16

What are the two cases where X inactivation is NOT random?

Answer 16

1. when there is an X with a structural abnormality

2. in X chromosome-autosome translocation

Question 17

What cells get inactivated in X chromosome translocations? The normal one or the balanced translocation?

Answer 17

The normal one getsi inactivated!! coz you don’t wanna inactivate the autosomal chromosome in the translocated chromosome

Question 18

What was the only way for females to be affected by DMD?

Answer 18

They had X chromosome balanced translocations.

–different autosome each time but always the same breakpoint on the X chromosome