Molecular and cytogenetics

Question 1

What is the detection rate for G banded chromosomes?

Answer 1

4% detection rate

Question 2

What is the detection rate for CMA?

Answer 2

15-20%

Question 3

Which type of microarray can detect regions of homozygosity?

Answer 3

SNP array

Question 4

What types of chromosome analyses can detect low level mosaicism?

Answer 4

Karyotype and SNP, not oligo arrays

Question 5

What is CMA a first line test for?

Answer 5

multiple congenital anomalies, non-syndromic delays/ID, autism, prenatal: US anomalies, multiple losses, POC

Question 6

What is the coefficient of inbreeding (F) for cousins?

Answer 6

1/16

Question 7

What percent of the genome of cousins is identical by descent?

Answer 7

6.25%

Question 8

What size of microarray deletions/duplications are likely to be benign?

Answer 8

<500kb 90-95% benign

Question 9

What size of a ROH is common in the general population (not in-bred)?

Answer 9

<3 mb

Question 10

What microarray results suggest a first or second degree parental relationship?

Answer 10

> 10% identical by descent with multiple regions of homozygosity of 2-5 mb

Question 11

What is the diagnostic yield of WES?

Answer 11

25-50% (~30%, ~40% for WGS)

Question 12

In what scenarios is WES recommended?

Answer 12

non-specific phenotypes, genetic heterogeneity (many genes), diagnostic odyssey/ other negative tests

Question 13

How often are secondary findings found in WES?

Answer 13

1-6%

Question 14

What regulates the cell cycle?

Answer 14

cyclins, and cyclin dependent kinases

Question 15

What is nondisjunction and when does it occur?

Answer 15

Mistake in separation of homologs in meiosis I, or between sister chromatids in meiosis II

Question 16

What are the DNA mismatch repair enzymes?

Answer 16

MLH1, MSH2, MSH6, PMS2

Question 17

What genes are involved with nucleotide excision repair?

Answer 17

the XP related genes

Question 18

What are the CGG repeat ranges for FMR1 related disease?

Answer 18

normal: 5-44, intermediate: 45-54, pre-mutation 55-200, Fragile X syndrome: >200

Question 19

What additionally regulates stability of the FMR1 regulatory sequence?

Answer 19

stable alleles have AGG repeat every 9-10 CGG repeats

Question 20

What types of blot are for DNA, RNA, proteins?

Answer 20

SNOW DROP:
Southern blot- DNA
Northern blot- RNA
Western blot- Protein

Question 21

What type of chromosome analysis requires actively dividing cells?

Answer 21

karyotype (and metaphase FISH)

Question 22

What is the difference between interphase and metaphase FISH?

Answer 22

interphase: can tell absence or presence but not location, faster than metaphase

metaphase: requires cell culturing, can show locations

Question 23

What are the recommendations for chromosome testing order in pregnancy ?

Answer 23

FISH first
if abnormal: karyotype next
if FISH normal: CMA next

note: prenatal FISH not considered diagnostic

Question 24

What is the risk of a child having an unbalanced translocation when a parent has an autosomal reciprocal translocation?

Answer 24

1-50%, depends

Question 25

What is the most common Robertsonian translocation (75%)?

Answer 25

13q;14q

Question 26

What is the risk for trisomy 21 with a 21q;21q isochromosome carrier?

Answer 26

100%

Question 27

What is the reason that T21, T18, and T13 are the most common liveborn trisomies?

Answer 27

These chromosomes have the lowest gene content

Question 28

What are the percent causes of T21 (maternal vs paternal, meiosis I vs II)?

Answer 28

85-90% maternal (75% MI, 25% MII) 3-5% paternal 4-5% Robertsonian 3-5% mitotic

Question 29

What is the risk of a liveborn infant with T21 at age 35?

Answer 29

1/385

Question 30

What are the percent causes of T18 (maternal vs paternal, meiosis I vs II)?

Answer 30

97% maternal (31% MI, 69% MII)

Question 31

How many cells are typically analyzed in a chromosome analysis?

Answer 31

~20, 50-100 if concerned for mosaicism

Question 32

What is a Philadelphia chromosome?

Answer 32

translocation between chromosome 9 and 22

Question 33

What are cells treated with to test for chromosome breakage syndromes and how does this work?

Answer 33

mitomycin C, causes chromatids to break and join to make tetraradials

Question 34

What is the resolution of FISH?

Answer 34

50-250 kb

Question 35

What percent of unbalanced translocations are inherited?

Answer 35

75% inherited, 25% de novo

Question 36

How are chromosomes labeled at the centromere?

Answer 36

p10/q10

Question 37

What is the risk of T21 or any chromosome aneuploidy at age 40?

Answer 37

T21 1/85 any 1/62

Question 38

What percent of early losses or still births are aneuploid?

Answer 38

50% of early losses 6-12% still births

Question 39

What percent of fetal T21 results in a live birth?

Answer 39

20%, 80% lost

Question 40

What is the recurrence risk of T21?

Answer 40

1-1.5%, higher in younger women (age related risk +1% >35)

Question 41

How does a ring chromosome form?

Answer 41

Terminal deletion of long and short arms, then fusion

Question 42

Are large or small percentric inversions more likely to result in a livebirth?

Answer 42

Large - cause small terminal del/dups, result in viable offspring with aneuploidy

Question 43

What fraction of small supernumerary chromosomes are familial?

Answer 43

1/3

Question 44

What is the likelihood of T21 if a mother or father is a carrier of a Robertsonian translocation?

Answer 44

maternal carrier: 10-15% risk paternal carrier: 3-5% risk (also seen 2% quoted)

Question 45

What percent of X chromosome genes escape X inactivation?

Answer 45

15%

Question 46

What percent of female carriers of XL conditions have symptoms?

Answer 46

10-15%

Question 47

Which of the following sex chromosome aneuplodies are associated with advanced maternal age: XXY, XXX, X0

Answer 47

associated with advanced maternal age: XXY, not: XXX, X0

Question 48

What percent of individuals with Turner syndrome have a 45, X karyotype?

Answer 48

45-50% monosomy X 15-25% mosaic 20% structural

Question 49

What percent of individuals with Turner syndrome go through puberty?

Answer 49

10%

Question 50

How many chromosomes with how many sister chromatids are present at: the start of meiosis? the end of meiosis I? the end of meiosis II? the end of mitosis?

Answer 50

the start of meiosis: 46 chromosomes, each with 2 sister chromatids the end of meiosis I: 23 chromosomes, each with 2 sister chromatids the end of meiosis II: 23 chromosomes, each with 1 sister chromatid the end of mitosis: 46 chromosomes, each with 1 sister chromatid

Question 51

What are the consequences (percentages) of nondisjunction in : mitosis? meiosis I? meiosis II?

Answer 51

mitosis: 50% trisomy, 50% monosomy meiosis I: 50% trisomy, 50% monosomy meiosis II: 50% normal, 25% trisomy, 25% monosomy

Question 52

What is the parent of origin for monosomy x?

Answer 52

80% paternal, 20% maternal

Question 53

What is the difference between isodisomy and heterodisomy and when do the corresponding errors occur?

Answer 53

Isodisomy: two of the same homolog from the same parent (meiosis II error or monosomy rescue) Heterodisomy: two different homologs from the same parent (meiosis I error or trisomy rescue)

Question 54

What percentage of SAB are due to triploidy?

Answer 54

6%

Question 55

Is diandric or digynic triploidy more common?

Answer 55

Diandric (85%) digynic (15%)

Question 56

What is the most common karyotype in chromosomal abnormal pregnancies losses?

Answer 56

45, X

Question 57

What are the causes of Patau syndrome?

Answer 57

80% T13, 20% 13;14 translocations

Question 58

What are the risks of a serious congenital anomaly in a de novo: Robertsonian translocation? Reciprocal balanced translocation? Inversion?

Answer 58

Robertsonian translocation: 3.7% Reciprocal balanced translocation: 6.1% Inversion: 9.4% RBI 3-6-9

Question 59

For the carrier of a balanced translocation carrier, what are the possible outcomes for adjacent-1 segregation?

Answer 59

all unbalanced gametes

Question 60

For the carrier of a balanced translocation, what are the possible outcomes for adjacent-2 segregation?

Answer 60

usually lethal, all unbalanced gametes (more unbalanced than adj-1)

Question 61

For the carrier of a balanced translocation carrier, what are the possible outcomes for alternate segregation?

Answer 61

50% normal, 50% balanced carrier

Question 62

What abnormality is seen on chromosome breakage studies for individuals with Fanconi anemia?

Answer 62

tetraradials

Question 63

What abnormality is seen on chromosome breakage studies for individuals with Bloom syndrome?

Answer 63

increased sister chromatid exchange

Question 64

What abnormality is seen on chromosome breakage studies for individuals with ataxia telangiectasia?

Answer 64

can have 7;14 rearrangements

Question 65

What are the possible outcomes of a paracentric inversion ?

Answer 65

balanced-normal, balanced with inversion, inviable with 2 centromeres, inviable with no centromeres