Sex Chromosome abnormalities

Question 1

How is gender determined is mammals?

Answer 1

The presence or absence of the Y chromosome

Question 2

What part of the Y chromosome is critical for determining gender?

Answer 2

SRY region

Question 3

What is the reason for an XY female or XX male?

Answer 3

1:20,000 of the time unequal crossing over occurs causing the SRY region to be placed on the X and removed from the Y

Question 4

What is a Barr Body?

Answer 4

An inactive X chromosome that consists of highly condensed heterochromatin and appears as a dark staining body in interphase

Question 5

What is the Lyon hypothesis?

Answer 5

Inactivation of either the paternal or maternal X occurs at the blastocyst stage and is random, resulting in XX mosaicism.

Depending on which X is inactivated, different X-linked traits will be expressed in different tissues or regions of the same tissue

Question 6

How common are sex chromosome abnormalities?

Answer 6

Among most common of all human genetic disorders, with an overall frequency of about 1/500 births

Question 7

What is Klinefelter syndrome?

Answer 7

47, XXY

Sexual development widely varies - sterile to normal

2/3 have learning disorders

Tall, lanky appearance with occasional breast enlargement

The more Xs, the more abnormal the phenotype

Question 8

Where does the error occur in Klinefelter?

Answer 8

1/2 are due to paternal M1 error

1/3 are due to maternal M1 error

Remainder are due to M2 errors

Question 9

What is 47 XYY syndrome?

Answer 9

Not associated with obvious abnormal phenotype

Patients may be tall but physically normal

Due to paternal nondisjunction at M2

Question 10

What is Trisomy X syndrome?

Answer 10

47, XXX

Normal fertility, but offspring are at increased risk of cytogenetic abnormalities

Above average stature but phenotypically normal

Significant deficit in performance on IQ tests, 70% have learning disorders

95% due to errors in maternal M1

Question 11

What is Turner syndrome?

Answer 11

45, X

Only monosomy compatible with life

Short stature, webbed neck, shield chest, infertile

Can be diagnosed during second trimester by hydrops or swelling localized to the neck

80% of cases due to loss of X or Y during paternal meiosis

Question 12

What are acentric chromosomes?

Answer 12

Chromosomes lacking a centromere

Question 13

What is translocation?

Answer 13

Transfer of genetic material from one chromosome to another

Question 14

What are reciprocal translocations?

Answer 14

breakage of at least 2 nonhomologous chromosomes with exchange of fragments

Balanced results in normal phenotype, increased risk of having abnormal offspring however

E.g. Philadelphia chromosome

Question 15

What is the Philadelphia chromosome?

Answer 15

Caused by reciprocal translocation betwen 22 and 9

Causes myelogenous leukemia

Question 16

What are Robertsonian translocations?

Answer 16

Reciprocal translocations between acrocentric chromosomes with the loss of the shor arms from both participating chromosomes

Reduces chromosome # to 45

Still considered balanced because the resulting loss includes only genes that are present in multiple copies throughout the genome

Question 17

What is the most common Robertsonian translocation?

Answer 17

Fusion of long arms of chromosomes 13 and 14

Question 18

Describe the segregation of Robersonian translocation during meiosis.

Answer 18

3 Possible ways of separating “homologues” at anaphase I (diagonal, vertical, horizontal) results in 6 different possible gametes

Question 19

What is translocation Down syndrome?

Answer 19

Offspring inherits two copies of chromosome 21 plus a translocation chromosome involving chromosome 21

Clinically the same as Trisomy 21

Parent with balanced translocation is at a high risk of having multiple affected children

Question 20

What are deletions and what are the three types?

Answer 20

Loss of a segment of a chromosome

Terminal

Interstitial

Ring chromosome

Question 21

What are terminal deletions and what two diseases are caused by them?

Answer 21

Deletion where the lost part includes an end of the chromosome

Wolf-Hierschhorn syndrome (4p-) - failure to thrive, mental retardation, very rare

Cri-du-chat (5p-) - microcephaly, micrognathia, high pitched cry, very rare

Question 22

What are Interstitial deletions?

Answer 22

Deletions resulting from two breaks on the same chromosome. Larger fragments can rejoin without the middle piece

Question 23

What are microdeletions and what disease is caused by this type?

Answer 23

Regions of loss cannot be detected by routine chromosome banding

Di George Syndrome

Question 24

What are Ring Chromosomes?

Answer 24

Formed when a break occurs on each arm of a chromosome leaving to sticky ends that reunite as a ring

Question 25

What are insertions?

Answer 25

Segment of one chromosome becomes inserted into another, can be balanced or unbalanced

Rare form of nonreciprocal translocation

Rare because requires three chromosomal breaks

Question 26

What is an Isochromosome?

Answer 26

Shows loss of one arm with duplication of another

Question 27

What is a duplication?

Answer 27

Can arise by a breakage process or mispairing following crossing over.

Results in partial trisomies

Question 28

What are inversions and what are the two types?

Answer 28

Two break rearrangement involving a single chromosome in which a segment is reversed in position.

Pericentric - involves centromere

Paracentric - does not involve centromere