Chromosome Structure and Method of Study

Question 1

cytogenetics

Answer 1

the study of chromosomes and cell division

cell culture, culture preparation, slide preparation

media mimics cell environment, add colcemid to prevent sindle fiber formation and prevents the cell from entering anaphase

cells accuulate in metaphase

not machine operated

Question 2

homologues

Answer 2

chromosome pairs, one from mom and one from dad

base pairs are not identical

Question 3

banding pattern

Answer 3

generated based on the used of a protease during processing

the protease digests scaffolding proteins at different places in the chromosomes

Question 4

chromosome structure

Answer 4

Short arm is called the p arm for “petite”

The long arm is called the q arm because it is the next letter of the alphabet

Chromosomes are always oriented with the short arm up

Question 5

chromosome types

Answer 5

metacentric - two distinct arms

submetacentric - two short arms

arcocentric - satellite arms

Question 6

arcocentic chromosomes

Answer 6

a special class of chromosomes with very small p arms, coprised of a large, tandm array of rDNA genes

satellites at the end of the stalks are “junk” DNA

length varies from person to person because loss of some satellites is not significant due to the highly repetitive nature

consists of chromosomes 13, 14, 15, 21, and 22

Question 7

ideogram

Answer 7

banding pattern for all chromosomes

every band given a number, starts from the centromere and moves outwards

divided into regions, bands, and sub-bands

Question 8

numerical chromosome abnormalities

Answer 8

euploid - exact multiple of haploid set

aneuploid - loss or gain of whole chromosomes (not a haploid set)

Question 9

structural chromosome abnormalities

Answer 9

terminal deletion, interstitial deletion, duplication, ring, isochromosome, paracentric inversion, pericentric inversion, translocation

Question 10

terminal deletion

Answer 10

a break in the chromosome and the rest is missing

Question 11

interstitial deletion

Answer 11

a piece in the middle gets deleted out

Question 12

duplicated

Answer 12

longer chromosome because of duplication

Question 13

ring chromosome

Answer 13

loss of ends of chromosomes, produce a circle to preserve itself fromdegradation

Question 14

isochromosome

Answer 14

q or p class, two of the same arms stuck together

Question 15

paracentric inversions

Answer 15

segment fliipped around, does not include centromere

Question 16

pericentric inversion

Answer 16

flipped segment, including centromere

Question 17

translocation

Answer 17

break on two chromosomes and swapping or material

Question 18

cytogenetic nomenclature

Answer 18

Question 19

Lyon hypothesis

Answer 19

in order to compensate for the extra dose of X in females, one gets inactivated

inactive chromosome is called the Barr body

X inactivation is random and occurs early in embryonic life

mediated by the XIST gene (X-inactivation specific transcript)

XIST gene on the X inactivation center (Xq13)

Question 20

stages of meiosis I (name the stages of prophase I)

Answer 20

prophase I, metaphase, I, anaphase I, telophase I

prophase I - leptotene, zygotene, pachytene, diplotene, diakinesis

Question 21

leptotene

Answer 21

chromosomes begin to condense

Question 22

zygotene

Answer 22

homologs align (synapse) and held together by synaptonemal complexes

Question 23

pachytene

Answer 23

each pair of homologs (bivalent) coils tightly, crossing-over occurs

Question 24

diplotene

Answer 24

homologs begin to separate, but remain attached at points of crossing-over (chiasmata)

Question 25

diakinesis

Answer 25

separation of homolog pairs, chromosomes are maximally condensed

Question 26

recombination

Answer 26

chiasmata are the points of crossing over

at least one corssing over per arm is required for proper segregation of chromosomes

only one sister chromatid is involved in each cross-over event

females have greater recombination than males

decreases near centromeres and increases near telomeres

Question 27

pseudoautosomal regions

Answer 27

X and Y chromosomes share two regions of homology, which undergo very high levels of genetic recombination

PAR1 is at distal and Xp and Yp

Par2 is in distal Xq and Yq

Question 28

Compare and contrast female and male meiosis.

Answer 28

one of the biggest differences is timing

females only have about 20 mitotic events before meiosis starts

males have hundreds of mitotic events before meiosis starts

Question 29

dictyotene

Answer 29

a stage in the first meiotic prohase where the egg gets arrested after the first female meiosis begins prenatally (3rd month)

Question 30

polyploidy

Answer 30

complete sets of extra chromosomes

ex. triploidy = 3N = 69/cell, tetraploidy = 4N = 92/cell, etc.

Question 31

Turner Syndrome

Answer 31

45, X - lack of second sex chromosome

Question 32

nondisjunction

Answer 32

failure of chromosomes or sister chromatids to separate

trisomy and monosomy can originate from meiotic or mitotic nondisjunction

most often maternal due to a MI error

errors increas in frequenct with maternal age

Question 33

balanced translocation pairing at meiosis

Answer 33

forms t structure, tetravalent orientation

alternate segregation will lead to a normal child

adjacent 1 and 2 will produce loss of part of one chromosome and the addition of another

Question 34

robertsonian translocation

Answer 34

a translocation between two acrocentric chromosomes, which results in the loss of the short arms of both chromosomes, but does not affect the DNA content of the long arms

individuals have normal karyotypes, but only 45 chromosomes

Question 35

meisosis segregation events for a robertsonian translocation

Answer 35

normal, balanced translocation, Down syndrome, monosomy 21, trisomy 14, monosomy 14

depends on the chromosomes involved, the only viable trisomies are 13, 18, and 21

the only monosomy that is viable is 45X

der(13;14) is the most common, 1 in 1500

Question 36

recombinations of inverted chromosomes

Answer 36

paracentric - unstable chromosomes due to acentric and dicentric chromosomes, can have recombination events that create on viable offspring

pericentric - results in stable chromosomes with blanced DNA content, can have recombination events that create on viable offspring

Question 37

karyotype resolution

Answer 37

the degree of banding that is visible dependingo n the condensation state of the DNA

band level is the measurement (typically 400-850)

the higher the number the greater the sensitivity

Question 38

FISH

Answer 38

fluorescence in situ hybridization

use a probe that ranges from 100kb to 1Mb with imbedded fluorescent molecule

probe can bind to target sequence and identify the presence of a particular DNA sequence

can use cells in interphase

downside is that you have to know what you’re looking for

Question 39

microdeletion syndroms

Answer 39

deletion of small region less than 5Mb, cannot be seen in normal karyotypes

only the resolution of FISH can detect these deletions

DiGeorge syndrom is one of the most common microdeletion diseases

Question 40

DiGeorge Syndrome

Answer 40

thymus hypo/aplasia

parathyroid hypo/aplasia

cardiovascular defects

other developmental defects

caused by a microdeletion on chromosome 22 (q11.2)

Question 41

array based comparative genomic hybridization

Answer 41

molecular cytogenetic method used to detect copy number imbalances

capable of genome-wide interrogation, objective method

two different colored probes hybridized to a plate, normal ratio is 0.8-1.2

control DNA made by combining the DNA of several different people

Question 42

high resolution tiling oligo array

Answer 42

array of probes centered around telomeres, centromeres, disease genes, and ~100kb interval coverage for each chromosome

Question 43

pitfalls of high resolution aCGH

Answer 43

cannot detect balanced rearangements and cannot distinguish mechanism

copy number variants (CNVs) - pathogenic, benign, unknown clinical significance

may misinterpret CNVs with this method because mechanism is unclear