Cytogenetics Flashcards
Chromosome Bands
- Light - GC Rich, Gene Rich
- Dark - AT Rick, Gene Poor
Trisomy 13
Patau Syndrome
IUGR
Microcephaly
Midline anomalies
Holoprosencephaly
Early lethality
Trisomy 18
Edwards Syndrome
Clubfoot or rocker-bottom feet
Clenched hand position with 2&5 over 3&4
Early lethal
Aneuploidy
Any chromosome can be affected
Majority with miscarriage < 12 weeks
Only liveborns: 13,18,21
Maternal age effect
>90% of trisomy result from maternal meiosis error
Monosomy not viable except 45,X Turners syndrome, which is usually result of paternal meiosis error
Mosaicism
Non disjunction during mitosis (instead of meiosis which leads to aneuploidy)
Different populations of cells throughout the body
Do not confuse with chimerism (most commonly two zygotes fuse to form one embryo)
Examples:
Pallister-Killian Syndrom
Emanuel Syndrome
Cat Eye Syndrome
Mosaic Turner syndrome
Turner Syndrome
45, X
can be mosaic
short stature, web neck, cystic hygroma, gonadal dyngenesis, coarctation of aorta
99% spontaneous abortion
typically paternal non-disjunction
Klinefelter syndrome
- 47 X,X,Y
- Clinical features
- tall stature
- gynecomastia
- small testes, infertility
- hypotonia, delayed motor skills
- learning disability, impaired social skills
- 1 / 1000
- 50% maternal, 50% paternal non-disconjuntion
XYY Syndrome
- Poly Y (47,XYY, 48, XYYY)
- Clinical features
- vary from barely noticeable to more severe
- learning disabilities, speech delay
- taller for some
- testicular failure for some
- hytonia
- ? immaturity/behanioral issues
- 1/1000 liveborn
- 50% maternal, 50% paternal meiosis error
Polysomy X Syndrome
- increasing numbers of sex chromosomes
- Karytotype
- female: 47, xxx, 48, xxxx, 49, xxxxx
- males: 48 xxyy, 48 xxxy, 49, xxxyyy, 49, xxyyy
- Clinical features
- learning disabilities
- hypotonia, delayed motor skills with increasing number of x chromosomes
- higher degree of facial dysmorphic features with increased numbers of X chromosomes
Lionization
Inactivation of 1 X chromosome,
randomly maternal and paternal source
Robertsonian Translocation
- Incidence 1 in 1000
- involves two acrocentric chromosomes: 13,14,15,21,22
- Loss of short arm of both chromosomes
- rob(13;14) is the most common
- chromosomes for trivalent during crossovers
- major segregations:
- alternate produces roughly equal frequencies of normal and balanced gametes
- adjacent 1 - produces 4 potential gametes, but both monosomes are lethal, trisomy 14 is lethal
- major segregations:
- Risk of trisomy 21:
- theoretical 33%
- empirical risk is 10-15% in female carrier, and 0-2% in male carrier
Deletion of 5p
Cri du Chat (cry of the cat)
development delay, speech, intellectual disability, dysmorphic facial features (hypertelorism, low-set ears, small jaw, rounded face)
Uniparental Disomy
- the inheritance of both homologous chromosomes (or chromosome segments) from one parent
- normal chromosome count
- detect with SNP microarray analysis or molecular genetic methylation status
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Genomic Imprinting
- Differential expression of genes on chromosome depending if inherited from mother or father, mainly occurring during embryogenesis
- can be reversible/reprogrammed
- Mechanisms:
- cannot be detected by chromosome or FISH analyses
- DNS modification by methylation
- acetylation of histones
Copy Number Variation (CNV)
- Submicroscopic segments of copy number loss or gain
- cannot be identified by G-banded chromosome analysis
- identified by cytogenetic microarray or whole genome sequencing
- inherited or somatic
- widely present in human genome and are a source of genetic variation in general population and human disease
- Examples
- Williams,
- Prader-Willi/Angelman
- Hereditary neuropathy with pressure palsies (HNPP) / Charcot-Marie-Tooth disease type 1A
- Smith-Mageni/Potocki-Lupski syndrome
- DiGeorge, Velocardiofacial syndrome (VCFS)
- Sotos syndrome
