Genetic Disorders Flashcards
Sickle Cell Disease
- autosomal recessive
- chromosome 11, single gene substitution
- 1/2500 affected
Cystic fibrosis
- autosomal recessive
- chromosome 7, single gene mutation - deletion of 3 bp
- 1/25 carriers, 1/2500 affected
Achondroplasia
- autosomal dominant
- mutation in the FGFR 3 gene
dont ever forget
population risk
the chances of someone not being affected at all is impossible, because there is always population risk
huntington’s disease
- autosomal dominant
- late onset
- chromosome 4, repetition of 3 nucleotides in the HTT gene
Duchenne muscular dystrophy (DMD)
- sex linked inheritance in men
- mutation of dystrophin protein that holds muscle together
haemophilia
- sex linked in men
which skips generations?
- sex linked (because daughters will only be carriers unless the father is affected and the mother is also a carrier)
- mitochondrial inheritance skips generations - can only be passed on by women, even if men were affected they cannot pass it on.
- autosomal dominant never skips generations
Leber Hereditary Optic Neuropathy (LHON)
- mitochondrial inheritance
- sudden loss of vision after 20-30 yrs
mitochondrial encephalopathy, lactic androsis, stroke (MELAS)
- mitochondrial inheritance
- dementia and vision loss
uniparental diploidity
- is a nonmendelian complex inheritance
- gynogenote: 2 maternal sets of 46 chromosomes - tumor in uterus containing hair teeth limbs but no placenta
- androgenote: 2 paternal sets of all 46 chromosomes - molar pregnancy of bubbly placenta with no sign of embryo
uniparental disomy
- nonmendelian complex inheritance
- angelman syndrome (AS)
- Prader willi syndrome (PWS)
angelman syndrome
- chromsome 15
- maternal chromosome has paternal imprint
- 2 paternal copies
cases:
- deletion of maternal copy (70%)
- Uniparental disomy of paternal copy (1-2%)
- imprinting of maternal by paternal copy - methylation of the maternal copy (2-4%)
- point mutation of the UBE3A gene in the maternal copy (10%)
Prader willi syndrome
- chromosome 15, same region as AS
- 2 maternal copies
causes:
1. deletion of paternal copy (70%)
2. UPD of maternal copies (25-30%)
3. imprinting - methylation of paternal copies (1-3%)
(no known point mutation)
Down syndrome
- trisomy 21
- incidence 1/650-700
- life expectancy 50-60 yrs
causes:
1. nondysjunction
2. unbalanced Robersonian translocation
3. mosaicism - issue with fetal development and not the gametes
Patau’s syndrome
- trisomy 13
- incidence 1/5000
- 5% die within the first month
causes:
1. nondysjunction
2. unbalanced Rbt translocation
Edward’s syndrome
- chromosome 18
- incidence 1/3000
- most die within the first month
causes:
1. nondysjuction
Klinefelter’s syndrome
- 47, XXY (extra X chromosome)
- incidence 1/1000
- only in men
- long limbs, infertile, mild learning difficulties, breast tissue
Turner’s syndrome
- 45, X (1 less X chromosome)
- incidence 1/5000-10,000
- most die before birth
- webbed neck, short, infertile, widely spaced nipples normal IQ and lifespan.
paracentric vs pericentrin inversion
paracentric is in the arms
pericentric includes the centromere
both are balanced.
reciprocal vs Rbt translocation
reciprocal is translocation btw 2 normal chromosomes
Rbt is fusion of the long arms and loss of the short arms of 2 acrocentric chromosomes.
reciprocal can be balanced or unbalanced
Rbt is unbalanced.
types of coding mutation
silent
missense
nonsense - missense that leads to a stop codon
frameshift
locus specific registers for genetic diseases
Clinvar - genomic variation and relationship to health Cosmic - somatic variants in cancer Decipher - development delay BRCA - breast cancer (global exchange) LOVD - leiden open variation database DMuDB - diagnostic mutation diseases
alamut in silico analysis tool
tool used to determine the location of missense location as well as its significance.
