Chromosomal abnormalities

Question 1

what is chromatin made up of?

Answer 1

DNA
non histone proteins
RNA
histones

Question 2

What are the histones and what do they form?

Answer 2

H1, H2A, H2B, H3, H4
H1 stabilises, there are two of each of the other 4 to form a histone octomer which interacts directly with the DNA and is what the H1 stabilises

Question 3

when do the chromosomes replicate in the cell cycle?

Answer 3

S phase

Question 4

What are the normal male and female chromosomes written as?

Answer 4

46, XY

46, XX

Question 5

what is a numerical chromosome abnormality?

Answer 5

a number of chromosomes other than 6

Question 6

what is a structural chromosome abnormality?

Answer 6

physical changes to one or more of the chromosomes

Question 7

what are the types of numerical chromosome abnormality and what are they?

Answer 7

polyploidy - gain of a whole haploid set of chromosomes, 3n (69,XXX)
anueploidy- loss or gain of whole chromosomes

Question 8

what are the types of aneuploidy?

Answer 8

monosomy - loss of one chromosome

trisomy - gain of one chromosome

Question 9

what can cause polyploidy?

Answer 9

polyspermy

Question 10

what can cause aneuploidy?

Answer 10

errors at cell division - non-disjunction

Question 11

what is non-disjunction?

Answer 11

failure of homologous chromosomes/sister chromatids to separate properly during cell division

Question 12

what happens if non-disjunction occurs during meiosis?

Answer 12

forms one gamete with a missing chromosome and one with an extra chromosome

Question 13

what happens if non-disjunction occurs during mitosis?

Answer 13

mosaicism

Question 14

what is mosaicism?

Answer 14

2 cell populations in an individual

Question 15

what does the degree of mosaicism depend on?

Answer 15

when error occured:
1st post zygotic division - no mosaicism looks like meiotic event
subsequent divisions - 3 cell lines, monosomy line usually lost as not compatible with life.

Question 16

what is anaphase lag? what can cause it? what happens to the lagging chromosome?

Answer 16

chromosome can be left behind at cell division.
defects in spindle function/attachment to chromosomes.
may be lost entirely.

Question 17

what are the two types of structural chromosome abnormalities? what happens in each?

Answer 17

Balanced - exchange/rearrangement of genetic material doesn’t cause any missing or extra genes
Unbalanced - exchange/rearrangement does cause missing/extra genes

Question 18

what are the types of chromosome mutations within 1 chromosome? what are they?

Answer 18

deletion - loss of genetic mat
duplication - some genetic mat is doubled
inversion - no loss but rearrangement of genetic mat
ring chromosome - loss of telemeres/ends of both arms and formation of ring
isochromosome -creation of 2 non identical chromosomes, 1 = combination of the 2 short arms and 1= combination of the 2 long arms

Question 19

what are the types of chromosome mutations with 2 chromosomes?

Answer 19

inversion
reciprocal translocation
robertsonian translocation

Question 20

what is inversion between 2 chromosomes?

Answer 20

no loss but rearrangement of genetic mat to a non homologous chromosome

Question 21

what is reciprocal translocation?

Answer 21

no loss but exchange of genetic mat between 2 non homologous chromosomes - 2 break arrangements
can be balanced/unbalanced

Question 22

what is robertsonian translocation?

Answer 22

rearrangement of genetic mat between 2 chromosomes: q arms of 2 acrocentric chromosomes combine to form one super chromosome with the loss of both p arms

Question 23

what is an acrocentric chromosome?

Answer 23

one with v short p arms

Question 24

what would a 21:21 translocation mean?

Answer 24

the 21 chromosomes are stuck together therefore when the cell divides, one cell will have both and one will have none.

Question 25

How can karyotypes be produced?

Answer 25

cut and paste of chromosome pictures into a systematically organised set of metaphase chromosomes organised in pairs.

Question 26

which is the biggest and which is the smallest chromosome?

Answer 26

1 and 22

Question 27

which pair are the sex chromosomes?

Answer 27

23

Question 28

what is karyotyping?

Answer 28

lab technique used to analyse chromosomes in order to look for any major chromosomal anomaly which may cause a genetic condition.

Question 29

what does the karyotyping formula start with? what does a +/- then a number indicate? what does a chromosome number then p/q and a +/- indicate?

Answer 29

the total number of chromosomes in the cell, followed by a comma, then the X then the Y chromosomes.
extra/missing chromosome.
extra/missing piece.

Question 30

what would 47,XX, +21 indicate?

Answer 30

an extra chromosome 21 (trisomy 21)

Question 31

what would be some reasons for referral for karyotyping?

Answer 31

prenatal screening (if family history of chromosomal abnormalities/abnormal ultra sound)
birth defects (malformations, mental retardation)
abnormal sexual development (klienfelter’s syndrome)
infertility
recurrent foetal loss
acquired abnormalities (leukaemia etc)

Question 32

How does FISH work?

Answer 32

single stranded nucleic acids are permitted to interact so that hybrids are formed by molecules with sufficiently similar complementary sequences.

Question 33

what can be determine through FISH?

Answer 33

the degree of sequence identity and therefore specific sequences/genes can be detected and located on a given chromosome.

Question 34

what does a microarray do and what can’t it detect?

Answer 34

examines whole genome at high resolution.

balanced rearrangements/mutations

Question 35

what does a microarray use?

Answer 35

patients DNA (not chromosomes) and compares them to a control DNA

Question 36

what are the disadvantages of microarray?

Answer 36

more expensive than karyotyping.
dont detect balanced arrangements.
mosaicism can be missed

Question 37

what can microarray be used for? why is it better for this?

Answer 37

NIPT - non invasive prenatal testing. testing for som single-gene disorders now approved
tests the free foetal DNA in the maternal plasma.
removes miscarriage risk as reduces need for invasive testing.

Question 38

what are chromosomes made up of?

Answer 38

chromatin