Sollars - Sex Chromosome Abnormalities

Question 1

Barr Body

What type of structural modification is this?

Answer 1

Inactive X Chromosome

Highly condensed, dark staining, heterochromatin

Tertiary structure modification

Question 2

What can serve as a diagnostic tool for number of X chromosomes?

Answer 2

Barr Bodies + 1 = Number of X chromosomes

Question 3

Lyon Hypothesis

Answer 3

Random X inactivation in somatic cells at the blastocyst stage; adult tissues are mosaic of inactivated X^M and X^P

In rare cases, large majority of one or the other may be inactivated–called Extreme or Unfavorable Lyonization

Question 4

What is the basis for the sex chromosomes being regulated differently than others?

Answer 4

Females (XX) should suffer from excess X-linked procducts, or males (X/Y) would be hemi-deficient in those gene products

This is not observed

Question 5

What is the critical region for determining gender?

What occurs 1:20,000 times?

Answer 5

SRY

Unequal crossing over can occur; SRY can be translocated to the X chromosome

Question 6

How many Barr bodies would the following have?

47,XXX

48,XXXY

Answer 6

2

2

Question 7

Are all genes inactivated on a Barr Body?

Answer 7

No, because Xo and XXY show abnormal development. Some X genes MUST escape inactivation.

Question 8

What is the overall frequency of sex chromosome abnormalities?

Answer 8

1/500 (common)

Question 9

Klinefelter Syndrome

Answer 9

47,XXY (XXXY, XXXXY)

1/1000

Tall, lanky appearance; Varying sexual development; more X’s = more abnormal

Nonmosaics always sterile

Question 10

47 XYY Syndrome

Answer 10

1/1000; 1/325 Tall males

Not associated w/obvious abnormal

Possible social disturbances; once throught to be criminal gene

Question 11

Trisomy X

Answer 11

47,XXX

.1% all females

Normal fertility; offspring at increased risk of cytogenetic abnormalities; usually tall; lower IQ

Question 12

Turner Syndrom

Answer 12

45, X

1/5-10,000

Only monosomy compatible with life

Short, webbed neck, shield chest, infertile

No barr body

All X-linked recessive alleles expressed

Question 13

If a female shows an X-linked recessive condition (Hemophiia ex), what can one suspect?

Answer 13

Turner Syndrome,

45,X

80% is caused by paternal

18% of all spon abortions are 45,X

Question 14

Acentric Chromosomes

Answer 14

Chromosomes lacking a centromere

These are LOST during chromosomal rearrangments (can’t be pulled apart)

Question 15

Translocation

Answer 15

Transfer of genetic material form one chromosome to another

Question 16

Reciprocal Translocation

Answer 16

Breakage of aleast 2 non-homologous chromosomes with exchange of fragments

Long arms of 11 and 22 relatively common

Philadelphia chromosome is an example (CML)

Carriers of balanced recip translocations rick of abnormal baby is 1-10%

Question 17

Robertsonian Translocation

Answer 17

Reciprocal translocation between acrocentric chromosomes

13,14,15 21,22

Reduces total chromosomes to 45

1/1000

Most common 13q14q fusion

Question 18

How can Robertsonian chromosomes separate during meiosis?

Answer 18

6 ways: Diagnal, Vertical, Horizontal

1 normal

1 balanced

4 unbalanced

Question 19

Translocation Down Syndrome

Answer 19

Offspring inherits normal 2 copies of chromosome 21, plus translocation chromosome involving chromosome 21

Clinical presentation same; unlike tris 21, parent with a balanced translocation hih risk of multiple affected children – 1/3 offspring

Question 20

Terminal Deletion

Interstitial Deletion

Ring Deletion

Answer 20

Loss of end of chromosome

Loss of interior portion of chromosome

Loss of ends; fusion in ring

Question 21

Wolf-Hirschhorn Syndrome

Answer 21

4p-

Severe mental retardation

Very rare; 1/50,000

Question 22

Cri Du Chat

Answer 22

5p-

Microcephaly, high pitched mewing cry, sever mental retardation; very rare

1/50,000

Question 23

Microdeletions

Answer 23

Not detectable by routine banding

Question 24

Di George Syndrome

Answer 24

Microdeletion of 22q11

Question 25

Why are insertions rare?

Answer 25

Requires 3 chromosome breaks

Question 26

Isochromosome

Answer 26

Loss of one arm w/duplication of other.

Most common is made up of 2x q-arms of X (20% of Turner syndromes)

Question 27

Duplication

Answer 27

Breaking or mispairing following crossing over; rresults in partial trisomies;

21q22.2 results in DS

Question 28

Inversion:

Peri

vs

Para

More dangerous?

Answer 28

Two break rearrangement involving single chromosome

Peri - Involved cetromere

Para - Does NOT involve centromere

Peri more risk