Geneticvs Of Chromsomal Abnormalities

Question 1

Cytogenetic analysis examples

Answer 1

Karyotyping

Chromosome banding

Fluorescence in situ Hybridization (FISH)

Comparative genomics hybridization (CGH)

Cytogenetic microarray (CMA)

Question 2

What are the two ways in meiosis to promote genetic diversity among gametes

Answer 2

late prophase = crossing over

Metaphase = bivalant separation independent (this allows each gametes to replicate its own unique genome)

Question 3

Comparative genomic hybridization (CGH) vs Cytogenomic Microarray (CMA)

Answer 3

CGH = can detect deletions and duplications shorter than 100kb ONLY
- doesnt detect balanced rearrangements

CMA = allows for detection of deletions and duplications of less than 20kb in size

• also detects loss of heterozygosity and uniparental disomy
• MUCH more sensitive but costs more

Question 4

Numerical chromosomal abnormalities

Answer 4

1) polyploid = presence of complete set of extra chromosomes in a cell
- not comparable with live usually

2) aneuploidy = cells/individual that contain either missing or additional chromosomes
- monosomy or trisomy are most common

Question 5

Causes of polyploidy

Answer 5

Dispermy = 1 egg + 2 spree cells = 3n always
most common cause

Fusion of the ovum and a polar body = 3n always

Meiosis failure = can be 3n or 4n

Fusion of two diploid zygotes = 4n always

usually any cause of polyploidy results in spontaneous abortion

Question 6

Aneuploidy

Answer 6

Always caused by nondisjunction (not proper Separation in metaphase) during meiosis 1 or meiosis 2
- results in a monosomy or a trisomy offspring

Examples of trisomy

• Down syndrome
• edwards
• klinefelter
• patau

Examples of monosomy
- Turner syndrome

only monosomy comparable with life = Turner syndrome

Proportion of trisomy undergoing spontaneous abortion

• patau = 95%
• edwards = 95%
• down syndroem = 80%

Question 7

Maternal age relationship with nondisjunction

Answer 7

As maternal age increases past 40 = higher rates of nondisjunction are known to occur
- paternal age is not linked to this

mechanism not understood though

Question 8

Robertsonian translocation

Answer 8

A chromosomal translocation that involves fusion of the long arms of two acrocentric chromosomes

• loss of short arms and causes 1 large chromosome to be formed
• always results in total chromosomes = 45
• *most common translocation**
• if you have a balanced Robertson translocation, you present with a normal phenotype and pass this on to progeny. However possessing a balanced translocation increases risks of unbalanced translocation in future generations

Can be unbalanced or balanced
- if unbalanced = trisomy, malformations or stillbirth are all possible

Question 9

Ring chromosomes

Answer 9

Are a special type of chromosomes that results in monosomy of that chromsome pair almost always
- if going to appear, usually seen in 14 or 22

Question 10

Isochromsomes

Answer 10

Special type of chromosome that is formed when a chromosome decides along an axis perpendicular to its usual axis of division
- this causes one chromosome to only have short arms and the other to only have long arms

Always substantially alters the chromsome information

Majority of autosomal isochromsomes = spontaneous abortion
exception = Turner syndrome (although this still does have high rates of abortion in the whomb

Question 11

Cri-du-chat syndrome

Answer 11

Caused by deletion of 5p on chromsome 5

Results in

• *cat like high pitched crying at birth
• *dysmorphic facial features (epicanthal folds, broad nasal bridge, downward palpebrae tissues)
• congential heart defects
• single palmar crease

Diagnosis = FISH is best

Question 12

Smith-Lemli -optic syndrome

Answer 12

Autosomal recessive disorder that results in a gene mutation at chromosome 11 (usually deletion)

Clinical features

• toe syndactyly
• single palmar crease
• random internal organ malformations
• dysmorphic facial features

always shows decreased cholesterol and elevated 7-dehydrocholesterol

Diagnosis = lab values and can also get FISH to confirm

Treatment = cholesterol replacement therpouy

Question 13

Uniparental disomy

Answer 13

Nondisjunction in both parental gametes which results in an embryo getting a full set from one parent only
- the other parent doesnt contribute anything

Seen in

• prader-willi = deletion of PATERNAL UBE3A on chromsome 15
• angelmann = deletion of MATERNAL UBE3A on chromsome 15

All disomy require FISH to diagnosis**