Human Genome and Karyotype

Question 1

during which stage of mitosis do chromatin condense into chromosomes

Answer 1

prophase (after replication)

after DNA replication, forms pair of sister chromatids

Question 2

what 2 principles increase genome complexity and size

Answer 2

1. duplication
2. incorporation (lateral transfer)

Question 3

what type of mutation is this:
GCATT —> GTACT

Answer 3

inversion (of CAT)

Question 4

genetic repeats can be substrates for abnormal recombination due to similar or identical nucleotide sequence. Which of these types is most likely to cause abnormal recombination?
a. long repeats (genes or blocks of genes)
b. short tandem repeats
c. transposons

Answer 4

long repeats more likely to cause abnormal recombination

recombination can cause inversions, duplications, or deletions

Question 5

gene recombination can cause ____, _____, or _____

Answer 5

inversions, duplications, deletions

Question 6

red-green color blindness is due to what kind of genetic mutation?

Answer 6

abnormal recombination of tandem repeat

long wavelength (red) and medium wavelength (green) photoreceptors are encoded by adjacent genes on X chromosome - they are tandem repeats

abnormal recombination during meiosis can delete one gene (green) from the X chromosome

Question 7

DiGeorge (aka Velocardiofacial syndrome), Prader-Willi, and Angelman syndrome are all due to what kind of genetic mutation

Answer 7

recombination occurring between large repeats that results in deletion of a block of DNA containing multiple genes —> complex phenotypes

DiGeorge: failure of pharyngeal pouch to develop, also parathyroid, thymus, and cardiac defects (deletion in chromosome 22)

Prader Willi and Angelman syndrome - both due to deletion in chromosome 15 (affecting genes that are imprinted)

Question 8

what does genetic anticipation refer to

Answer 8

short tandem repeat expansion occurring de novo in sperm/egg

results in heritable disease phenotype within single generation

more expansions = more severe disease

examples: Huntington’s, Kennedy’s, myotonic dystrophy, Fragile X

Question 9

what enzyme is needed to generate a retrotransposon (type I transposon)

Answer 9

RETROtransposons need RT - creates ds cDNA from ssRNA

these can be caused by transposons: cystic fibrosis, hemophilia A, X-linked dystonia-parkinsonism

Question 10

in what contexts should you consider a possible chromosome abnormality? (4)

Answer 10

1. problems with physical or mental development of fetus or child
2. infertility, spontaneous abortion, stillbirth
3. pregnancy in women over 35
4. cancer

Question 11

do you need to know the location of a chromosomal abnormality to identify it with FISH?

Answer 11

YES: need to design a specific probe

FISH = fluorescent in situ hybridization

detects changes too small to see in G-banding

however, only detects presence/absence/ position of DNA to which probe binds (cannot rule out genetic defect elsewhere)

Question 12

what can comparative genomic hybridization (CGH) detect?

Answer 12

deletions or duplications, even if location is unknown

Question 13

when karyotyping with G-banding, chromosomes are incubated with _____, which arrests the cells in metaphase. They are then stained with ____ dye

Answer 13

colchicine - disrupts tubulin- dependent spindle function

Giemsa dye (heterochromatin are darker)

Question 14

how do you identify chromosomes with G banding

Answer 14

size (1 largest, 22 smallest)
centromere position
banding pattern (of hetero/euchromatin)

Question 15

what type of genetic material is contained in centromeres

Answer 15

satellite DNA (tandem repeats of non coding DNA)

can use centromere to identify chromosomes, esp when there are chromosomal abnormalities

Question 16

how are chromosome bands numbered

Answer 16

outward from the centromere, with arm (p, petite, or q) specified

Question 17

which has a higher resolution, interphase or metaphase FISH?

Answer 17

interphase, because DNA is not condensed

can be done directly on clinical samples (ex: prenatal diagnosis), no need to culture cells to amplify number

Question 18

what does comparative genome hybridization (CGH) determine overall

Answer 18

ability of test genome to hybridize to reference genome

on a microarray

identifies deletions and duplications

Question 19

which trisomies are not lethal

what X-linked aneuploidies are not lethal

Answer 19

trisomies: 13, 18, 21

45, X (Turner) - only non lethal monosomy

47, XXY (Kleinfelter)

Question 20

most common translocations are between _____

Answer 20

acrocentric (small p arm) autosomal chromosomes

considered balanced if no genetic material is lost or not significant phenotype arises

Question 21

what kind of chromosomal abnormality is this:
46, XY, t(1;3)(q31;q24)

Answer 21

t = translocation
between chromosomes 1 and 3
breaks occur at q31 (chromosome 1) and q24 (chromosome 3)

Question 22

Robertsonian translocation

Answer 22

rare translocation in which break points occur within centromeres of acrocentric chromosomes and they fuse (p arms are lost)

pairing of homologous chromosomes during metaphase of meiosis will occur between 3 chromosomes (2 normal and 1 translocation)

Question 23

what are the possible outcomes for a fetus with iso chromosome 21 (q arms of both copies fused, p arms fused)

Answer 23

trisomy 21 - lethal or Down syndrome

monosomy 21 - lethal

gametes receive either i21q or no chromosome 21

Question 24

pericentric vs paracentric inversions

Answer 24

both are inversions including the centromere

pericentric - break in p and q arms
paracentric - both breaks in same arm

Question 25

if you wanted to detect a 1.5-3Mb deletion in 22q11.2, which would you use?
a. interphase FISH
b. metaphase FISH

Answer 25

interphase FISH

metaphase FISH detects changes in centrosomes