X-inactivation and dosage compensation

Question 1

The process by which the dosage of X – linked genes is balanced between two Xs in females and one X in males.

Answer 1

X inactivation

Question 2

T/F. For each somatic cell, it is random whether the paternal X or maternal X is inactivated, and it changes for subsequent descendants of that cell.

Answer 2

False. Paternal or maternal X inactivation is imprinted for subsequent descendants of that cell.

Question 3

X inactivation is common to all placental mammals and, in humans, as evidenced by the appearance of the _____. X inactivation begins as early as the ___ stage.

Answer 3

XIST (X - inactivation - specific transcript) RNA; 8-cell

Question 4

T/F. X inactivation only occurs in somatic cells, as in the germ line both X chromosomes need to remain active.

Answer 4

True.

Question 5

T/F. Product levels for most genes on the X chromosome are similar in females and males where the single X always remains active, except in primary spermatocytes where it becomes part of the condensed sex body.

Answer 5

True. X inactivation inactivates one of the X chromosomes in females

Question 6

While most genes carried in the human X chromosome are inactivated during X inactivation, some genes including the ones located within the ____, ____ and ___, located at the tips of Xp and Xq respectively.

Answer 6

blocks of sequence identity between the X and Y; PAR1 and PAR2

Question 7

Deficiency of the ____, w/c encodes a transcription factor important for chondrocyte function, can cause isolated short stature.

Answer 7

short stature homeobox gene
(SHOX)

Question 8

There are at least ____ genes within PAR1 & ____ within PAR2, all of which escape X - inactivation with the exception of the two most proximal genes within ____.

Answer 8

25; 4; PAR2

Question 9

Deficiency of SHOX can result in skeletal malformations in addition to short stature, causing _____ associated with the so - called _____ of the forearm, and its more severe homozygous (or compound heterozygous) form, _____.

Answer 9

Léri – Weill dyschondrosteosis; Madelung deformity; Langer mesomelic dysplasia

Question 10

Loss of one copy (causing haploinsufficiency, i.e. inadequate protein product) of the SHOX gene is also thought to be responsible for some of the features of ____.

Answer 10

Turner syndrome

Question 11

This locus is only active in the inactive X and plays an important role in regulating the inactivation process itself.

Answer 11

X-inactive specific transcript (XIST)

Question 12

It encodes long non - coding RNA molecules, w/c coat the chromosome and initiate transcriptional silencing.

Answer 12

X-inactive specific transcript (XIST)

Question 13

The mechanism by w/c XIST spreads along the X chromosome is unclear but may involve repeated sequences on the X chromosome, such as the many ____ acting as ‘boosters ’ .

Answer 13

long interspersed elements (LINEs)

Question 13

The silencing by XIST appears to depend on repeated sequences in its 5 ′ end that each fold into two ____ RNA structures.

Answer 13

stem – loop

Question 14

In the silencing by XIST, the loop forming repeated sequences near the 5’ end permit direct or indirect binding of repressor proteins such as those of the ____ group.

Answer 14

polycomb

Question 15

Maintenance of X chromosome inactivation throughout subsequent cell divisions involves other factors including ____ and also DNA ____.

Answer 15

hypoacetylation of histone H4; methylation

Question 16

T/F. CpG islands of housekeeping genes on the active X are hypermethylated, while the reverse is true of the inactive X.

Answer 16

False. DNA methylation of CpG islands maintains inactivation of the inactive X.

Question 17

T/F. The inactive X completes its replication earlier in mitosis than any of the other chromosomes, and thus is out of phase with the active X.

Answer 17

False. inactive X completes replication later in mitosis.

Question 18

T/F. In females w/ loss of material from one X chromosome, the structurally normal X is preferentially inactivated.

Answer 18

False. Abnormal chromosome is preferentially inactivated.

Question 19

T/F. In females with X-autosome translocation, the normal X is preferentially inactivated.

Answer 19

True.

Question 20

In females with X-autosome translocation, inactivation of the X-autosome hybrid may lead to autosomal monosomy.

Answer 20

True.

Question 21

The inactive X remains condensed during most of interphase and is visible in a variable proportion of the nuclei in most tissues as a densely stained mass of chromatin known as the ____.

Answer 21

Barr body or X chromatin

Question 21

Inactivation center is located in ___.

Answer 21

Xq13

Question 22

T/F. If a cell has more than two X chromosomes, then the extra ones are also inactivated and more than one Barr body will be seen in some cells.

Answer 22

True

Question 23

What is the maximum number of Barr bodies per cell?

Answer 23

one less than the total number of X chromosomes in the karyotype

Question 24

The sex chromatin may also be seen in 1 – 10% of female neutrophils as a small ____.

Answer 24

drumstick

Question 25

Females would have a homogenous cells with with only one X chromosomes – paternal or maternal – being inactivated constantly among all cells.

Answer 25

False. Due to randomness of inactivation, a female would have a mixture of cells, some of which have an active paternal X chromosome and some of which have an active maternal X chromosome.

Question 25

T/F. Patchy expression of mutant X-linked genes in carrier females is expected.

Answer 25

True. Due to mixture of cells with inactivated paternal or maternal X chromosome.