Genetics Lecture II

Question 1

cytogenetics

Answer 1

study of inheritance related to chromosome formation

Question 2

constitutional

Answer 2

abnormal chromosomes that are inherited rather than acquired

Question 3

Two categories of abnormal chromosomes

Answer 3

structural and numerical abnormalities

Question 4

Historically chromosome rearrangements have involved large/small regions because they were detected by karyotypes/FISH

Answer 4

large; karyotypes

Question 5

Karyotype (G-banding)

Answer 5

older technique used to detect gains and losses of entire chromosome and fairly large regions of the chromosome

strengths: visualize entire genome
weakness: poor resolution, takes time, cells must be viable and usually from metaphase

Question 6

Why do chromosome abnormalities result in disease?

Answer 6

up-regulate or down-regulate gene products, alter the gene product itself, fusion protein (different protein)

Question 7

What phenotypes are typically associated with chromosome abnormalities?

Answer 7

• cancer
• ID
• dysmorphic characteristics
• abnormal development (birth defects)
• early termination pregnancy
• infertility
• early deaths (spontaneous abortions/stillbirths)
• normal (personal or family history with abnormal offspring, miscarriages and or infertility)

Question 8

balanced structural chromosome rearrangements

Answer 8

normal/balanced phenotype; total number of chromosomes changes; translocation produces abnormal karyotype ex. robertsonian translocation “45, XY, rob”

Question 9

balanced reciprocal translocation

Answer 9

normal phenotype; total number of chromosomes remain unchanged but abnormal karyotype persists

Question 10

unbalanced

Answer 10

abnormal phenotype and abnormal karyotype

Question 11

unbalanced robertsonian translocation definition and how many chromosomes

Answer 11

abnormal phenotype and abnormal karyotype

46 CHROMOSOMES

Question 12

individuals with a personal or family history of clinically abnormal offspring, miscarriage and or infertility often carry

Answer 12

balanced structural chromosomes rearrangements

Question 13

fluorescent in situ hybridization

Answer 13

steps: denature to single strand, probe matching sequences, incubate, wash
strengths: mechanism, increased resolution, identifies patients with micro-deletions and micro-duplications
weakness: very specific, needs clinical diagnosis to be able to pull the right test

Question 14

example of syndrome that FISH would be used for

Answer 14

DiGeroge Syndrome
abnormal: facial features (prominent nose and small eyes and ears), hypocalcemia, immune deficiency, psychiatric disorders, heart abnormalities

Question 15

q(11.21)

Answer 15

deletion seen in 25% of patients with DiGeorge Syndrome, identified by FISH

Question 16

Chromosome Microarray Technology

Answer 16

strengths: viable cells, high resolution
1. consanguinity: mating between relatives
2. uniparental disomy: genetic material passed from one parent
weakness: whole genome, expensive, takes time
Affymetrix CytoScan HD Single Nucleotide Polymorphism (SNP) Array

Question 17

Affymetrix CytoScan HD SNP contains how many probes

Answer 17

2.7 million probes

Question 18

uniparental disomy

Answer 18

long stretches of homozygosity, both copies of an allele passed from one parent, can lead to transient neonatal diabetes

Question 19

consanguinity

Answer 19

long stretches of homozygosity, mating between relatives; increase recessive condition and recessive genes

Question 20

microarray technology can be used to detect

Answer 20

cryptic imbalances

Question 21

two possible SNP allele

Answer 21

A-T A allele

G-C B allele

Question 22

what will SNP allele combinations look like for increased consanguinity or uniparental disomy

Answer 22

less AB and more AA or BB

Question 23

First Tier Test

Answer 23

microarrary technology (AffyxMetrix CytoScan HD SNP) will detect most of the cytogenetic abnormalities (except balanced rearrangements or low levels of mosaicism) but has also increased number of variant of unclear clinical significance