Molecular and cytogenetics Flashcards
What is the detection rate for G banded chromosomes?
4% detection rate
What is the detection rate for CMA?
15-20%
Which type of microarray can detect regions of homozygosity?
SNP array
What types of chromosome analyses can detect low level mosaicism?
Karyotype and SNP, not oligo arrays
What is CMA a first line test for?
multiple congenital anomalies, non-syndromic delays/ID, autism, prenatal: US anomalies, multiple losses, POC
What is the coefficient of inbreeding (F) for cousins?
1/16
What percent of the genome of cousins is identical by descent?
6.25%
What size of microarray deletions/duplications are likely to be benign?
<500kb 90-95% benign
What size of a ROH is common in the general population (not in-bred)?
<3 mb
What microarray results suggest a first or second degree parental relationship?
> 10% identical by descent with multiple regions of homozygosity of 2-5 mb
What is the diagnostic yield of WES?
25-50% (~30%, ~40% for WGS)
In what scenarios is WES recommended?
non-specific phenotypes, genetic heterogeneity (many genes), diagnostic odyssey/ other negative tests
How often are secondary findings found in WES?
1-6%
What regulates the cell cycle?
cyclins, and cyclin dependent kinases
What is nondisjunction and when does it occur?
Mistake in separation of homologs in meiosis I, or between sister chromatids in meiosis II
What are the DNA mismatch repair enzymes?
MLH1, MSH2, MSH6, PMS2
What genes are involved with nucleotide excision repair?
the XP related genes
What are the CGG repeat ranges for FMR1 related disease?
normal: 5-44, intermediate: 45-54, pre-mutation 55-200, Fragile X syndrome: >200
What additionally regulates stability of the FMR1 regulatory sequence?
stable alleles have AGG repeat every 9-10 CGG repeats
What types of blot are for DNA, RNA, proteins?
SNOW DROP:
Southern blot- DNA
Northern blot- RNA
Western blot- Protein
What type of chromosome analysis requires actively dividing cells?
karyotype (and metaphase FISH)
What is the difference between interphase and metaphase FISH?
interphase: can tell absence or presence but not location, faster than metaphase
metaphase: requires cell culturing, can show locations
What are the recommendations for chromosome testing order in pregnancy ?
FISH first
if abnormal: karyotype next
if FISH normal: CMA next
note: prenatal FISH not considered diagnostic
What is the risk of a child having an unbalanced translocation when a parent has an autosomal reciprocal translocation?
1-50%, depends
What is the most common Robertsonian translocation (75%)?
13q;14q
What is the risk for trisomy 21 with a 21q;21q isochromosome carrier?
100%
What is the reason that T21, T18, and T13 are the most common liveborn trisomies?
These chromosomes have the lowest gene content
What are the percent causes of T21 (maternal vs paternal, meiosis I vs II)?
85-90% maternal
(75% MI, 25% MII)
3-5% paternal
4-5% Robertsonian
3-5% mitotic
What is the risk of a liveborn infant with T21 at age 35?
1/385
What are the percent causes of T18 (maternal vs paternal, meiosis I vs II)?
97% maternal
(31% MI, 69% MII)
How many cells are typically analyzed in a chromosome analysis?
~20, 50-100 if concerned for mosaicism
What is a Philadelphia chromosome?
translocation between chromosome 9 and 22
What are cells treated with to test for chromosome breakage syndromes and how does this work?
mitomycin C, causes chromatids to break and join to make tetraradials
What is the resolution of FISH?
50-250 kb
What percent of unbalanced translocations are inherited?
75% inherited, 25% de novo
How are chromosomes labeled at the centromere?
p10/q10
What is the risk of T21 or any chromosome aneuploidy at age 40?
T21 1/85
any 1/62
What percent of early losses or still births are aneuploid?
50% of early losses
6-12% still births
What percent of fetal T21 results in a live birth?
20%, 80% lost
What is the recurrence risk of T21?
1-1.5%, higher in younger women
(age related risk +1% >35)
How does a ring chromosome form?
Terminal deletion of long and short arms, then fusion
Are large or small percentric inversions more likely to result in a livebirth?
Large - cause small terminal del/dups, result in viable offspring with aneuploidy
What fraction of small supernumerary chromosomes are familial?
1/3
What is the likelihood of T21 if a mother or father is a carrier of a Robertsonian translocation?
maternal carrier: 10-15% risk
paternal carrier: 3-5% risk (also seen 2% quoted)
What percent of X chromosome genes escape X inactivation?
15%
What percent of female carriers of XL conditions have symptoms?
10-15%
Which of the following sex chromosome aneuplodies are associated with advanced maternal age: XXY, XXX, X0
associated with advanced maternal age: XXY,
not: XXX, X0
What percent of individuals with Turner syndrome have a 45, X karyotype?
45-50% monosomy X
15-25% mosaic
20% structural
What percent of individuals with Turner syndrome go through puberty?
10%
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?
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
What are the consequences (percentages) of nondisjunction in :
mitosis?
meiosis I?
meiosis II?
mitosis: 50% trisomy, 50% monosomy
meiosis I: 50% trisomy, 50% monosomy
meiosis II: 50% normal, 25% trisomy, 25% monosomy
What is the parent of origin for monosomy x?
80% paternal, 20% maternal
What is the difference between isodisomy and heterodisomy and when do the corresponding errors occur?
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)
What percentage of SAB are due to triploidy?
6%
Is diandric or digynic triploidy more common?
Diandric (85%)
digynic (15%)
What is the most common karyotype in chromosomal abnormal pregnancies losses?
45, X
What are the causes of Patau syndrome?
80% T13, 20% 13;14 translocations
What are the risks of a serious congenital anomaly in a de novo:
Robertsonian translocation?
Reciprocal balanced translocation?
Inversion?
Robertsonian translocation: 3.7%
Reciprocal balanced translocation: 6.1%
Inversion: 9.4%
RBI 3-6-9
For the carrier of a balanced translocation carrier, what are the possible outcomes for adjacent-1 segregation?
all unbalanced gametes
For the carrier of a balanced translocation, what are the possible outcomes for adjacent-2 segregation?
usually lethal, all unbalanced gametes (more unbalanced than adj-1)
For the carrier of a balanced translocation carrier, what are the possible outcomes for alternate segregation?
50% normal, 50% balanced carrier
What abnormality is seen on chromosome breakage studies for individuals with Fanconi anemia?
tetraradials
What abnormality is seen on chromosome breakage studies for individuals with Bloom syndrome?
increased sister chromatid exchange
What abnormality is seen on chromosome breakage studies for individuals with ataxia telangiectasia?
can have 7;14 rearrangements
What are the possible outcomes of a paracentric inversion ?
balanced-normal, balanced with inversion, inviable with 2 centromeres, inviable with no centromeres
