Cytogenetics - human chromosomes and disorders

Question 1

what are microsatellites?

Answer 1

repeated units of DNA

Question 2

what is an aneuploidy?

Answer 2

one or more individual chromosomes in extra copy or missing

Question 3

how many chromosomes do humans have?

Answer 3

46 chromosomes

(23 from mom and 23 from dad)

Question 4

in a normal karyotype picture, what do the dark bands represent? What do the light bands represent?

Answer 4

dark bands= heterochromatin (AT rich and gene poor region)

light band = euchromatin (GC rich and gene rich)

Question 5

describe the banding nomenclature of chromosomes

ex) 1p13.3

Answer 5

1p13.3 refers to the

1st chromosome

p= short arm of chromosome

13= region of the chromosome

3= sub-band of region

Question 6

what are the two basic types of chromosome abnormalities?

Answer 6

1. numberical aberrations
   
   1. like trisomy (47 chromosomes) or monsomy (45 chromosomes)
2. structural aberrations
   
   1. involving 1 chromosome- deletion , duplications, inversion, ring chromosome
   2. involving 2 chromosomes - translocations

Question 7

how does aneuploidy arise?

Answer 7

from chromosomal non-disjunction

• failure of homologous chromosomes to separate and segregate normally in either mitosis or meiosis
• when it occurs in meiosis, non-disjunction results in imbalances gametes - should one of those gametes fertilize, all cells derived from the resulting embryo will have a chromosome imbalance
• when it occurs in mitosis - nondisjunction produces two cell-lineages derived from a single zygote (known as mosaicism)= less severe syndrome

Question 8

when does non-disjunction occur in meiosis?

Answer 8

non-disjunction can occur in either the first or second meiotic division and consequences are different

first = gametes contain either both parental chromosomes which failed to separate or neither

second = gametes contian two identical copies of the same chromosome or neither

zygotes will either bet monosomic or trisomic

Question 9

what are some clinical features of down syndrome?

Answer 9

• developmental delay
• variable intellectual disability
• characteristic facial features
• congenital heart defects
• premature ageing
• risk of leukaemia

Question 10

what is the incidence of trisomy 21?

Answer 10

1/650 live-births (about 50% spontaneous abortions)

risk increases with maternal age

30 yr= 1/900

36 year= 1/300

40 yr= 1/100

44 yr = 1/40

Question 11

What is trisomy 18?

Answer 11

Ewards Syndrome= rocker-bottom feet, usually die within 1 year

Question 12

What is Trisomy 13?

Answer 12

Patau syndrome = polydactyly, death usually within 1 year

Question 13

what is monosomy X?

Answer 13

Turner syndrome

Question 14

what is kleinefelter syndrome?

Answer 14

extra x chromosome male

Question 15

what is a reciprocal translocation of chromosome?

Answer 15

where two chromosomes swap genetic material

Question 16

what is a robersonian translocation?

Answer 16

where part two chromosomes combine

Question 17

what test is used to detect microdeletion syndromes?

Answer 17

fluorescence in situ hybridization = FISH

• also used to detect estrogen dependent cancer -

Question 19

what does ‘imprinting’ mean in genetics ?

Answer 19

different expression of the same chromosomal region depending on whether the region was inhertied from mom or dad

*DNA methylation differences responsible for altered gene expression*

Question 20

what is an Array CGH used for?

Answer 20

it is the ‘gold standard ‘ for future genetic testing

detects highly subtle gain or loss of genetic material - significantly more sensitive than G-band karyotyping

-same resolution as FISH but is genome-wide detection method

Question 21

when do we use G-band karyotyping, FISH or Array CGH?

Answer 21

large chromosome syndromes = g band karyotyping or FISH

translocations = g band karyotyping

microdeletions = FISH

unexplained developmental delay or congenital malformations = Array CGH