Robinson Lectures Flashcards
Smallest human chromosome
Chromosome 21
What is unique about mouse chromosomes?
All acrocentric
What is unique about Rhea Americana chromosomes?
Many microsomes
Down syndrome genotype
47, +21
Klinefelter syndrome genotype
47, XXY
Edwards syndrome phenotype
47, +18
Patau syndrome genotype
47, +13
Incidence of trisomy 21 at conception and birth
C: 1/200
B: 1/800
Incidence of trisomy 18 at conception and birth
C: 1/500
B: 1/5000
Incidence of Klinefelter syndrome at conception and birth
C: 1/500
B: 1/1000
Incidence of trisomy 13 at conception and birth
C: 1/500
B: 1/10,000-20,000
Incidence of triploidy at conception and birth
C:1/100
B: 1/60,000
Turner syndrome genotype
45, X
Incidence of Turner syndrome at conception and birth
C: 1/100
B: 1/10,000
Why are sex chromosome abnormalities better tolerated than autosomal chromosome abnormalities?
- Not many genes carried on the Y chromosome
2. X-chromosome inactivation
Which trisomies are rare in clinical pregnancies?
1, 11, 19
Which monosomies are rare in clinical pregnancies?
All
Which trisomies are commonly found in miscarriages?
All (incl. 47, XXX and 47, XXY)
Which monosomies are commonly found in miscarriages?
45, X
Which trisomies can survive to term?
13, 18, 21
47, XXY
47, XYY
47, XXX
Which monosomies can survive to term?
45, X (rarely)
Which polyploidy can survive to term?
Triploidy, rarely
What is the leading cause of miscarriages?
Chromosome abnormalities
What is the combined incidence of trisomy at birth?
1/300
Are females with Turner syndrome fertile?
No, streaked ovaries
Are 47, XXX females fertile?
Yes
Are Klinefelter (47, XXY) males fertile?
No
Are 47, XYY males fertile?
Yes
Which chromosomes can be involved in Robertsonian translocations?
Acrocentric chromosomes (13, 14, 15, 21, and 22)
DiGeorge syndrome genotype
Deletion in chromosome 22
Main disadvantage of targeted cytogenetic approaches
Need a probe specific to the sequence you are testing
Main disadvantages of array-based cytogenetic approaches
Expensive
Detect meaningless changes
Cannot detect balanced or structural changes
Which chromosomal abnormality was found to be a main cause of chronic myelogenous leukaemia?
Translocation between chromosome 22 and chromosome 9
William’s syndrome genotype
Recurrent deletion in chromosome 7
DiGeorge syndrome genotype
Recurrent deletion on chromosome 22
What gene is missing in Williams syndrome?
Elastin gene
Which cytogenetic technique can be used to detect deletions?
FISH
Which cytogenetic technique can be used to detect duplications?
FISH (use in interphase cells)
Which cytogenetic technique can detect complex rearrangements?
M-FISH or SKY
Muntjac chromosomes are unique because
Closely related species have very different numbers of chromosomes
aCGH vs SNP array
aCGH: requires control DNA; cannot detect polyploidy or balanced translocations
SNP array: doesn’t require control DNA; can detect polyploidy, parental origin, or loss of heterozygosity
CMA vs G-banding
CMA: can detect smaller changes; don’t need to culture blood; can use DNA samples that were preserved; can have ambiguous/false positives; more expensive
G-banding: can’t detect as small changes; need to culture blood (takes more time); cheaper
Size of microscopic structural variants
> 3MB (visible with G-banding)
Size of submicroscopic structural variants
50 bp - 3 MB
Which regions of the genome contain lots of CNVs?
Pericentromeric and subtelomeric regions
Which genes are least affected by CNVs and why?
Genes associated with diseases (select for a certain copy number)
How do CNVs differ in individuals with a disease compared to healthy controls?
Individuals with disease have on average larger CNVs
How does one know if a CNV is pathogenic?
More likely pathogenic: De novo, larger size (>1MB), includes a gene that is affected by dosage, rare, similar cases in database
Less likely pathogenic: Inherited from an unaffected patient, small size, few genes disrupted, common in the population (including healthy individuals)
What percentage of developmental delay do de novo CNVs account for?
14%
Where do most errors to trisomy occur?
Maternal M1
Where is meiosis arrested in females?
Diplotene of prophase 1
What are 3 possible causes of meiosis errors?
Failure of recombination or SC formation; failure of cohesin at sister chromatids or chiasmata; failure of spindle
How common are lethal chromosome abnormalities in humans at conception?
1/5
What aspects of chromosomes are conserved across species?
Centromere, telomere
Robertsonian translocation frequency in population
1/800
Genotype of chimpanzee
2n = 48
What is the function of cot-1 DNA in M-FISH/SKY?
Blocks out repetitive regions in the genome so you don’t get cross-hybridization for repeats on different chromosomes
What is the genotype of Sewyer syndrome?
46, XY with no SRY region
