Genetic Heterogeneity Flashcards
What is genetic heterogeneity?
More than one gene is mutated >>> causes particular phenotype
Examples of genetic heterogeneity: Autosomal dominant (AD)
Autosomal dominant (AD) only
- Autosomal dominant polycystic kidney disease
- Hypertrophic obstructive cardiomyopathy
- Noonan’s syndrome
- Tuberous sclerosis
Examples of genetic heterogeneity: Autosomal dominant (AD) with reduced penetrance
Autosomal dominant (AD) with reduced penetrance
- Hereditary non-polyposis colon cancer
- Hereditary breast cancer
- Hereditary ovarian cancer
Examples of genetic heterogeneity: Autosomal dominant or recessive (AD or AR)
Autosomal dominant or recessive (AD or AR)
- Long QT syndrome
Examples of genetic heterogeneity: AR or AD or X-linked
AR, or AD, or X-linked
- Alport syndrome
- Retinitis pigmentosa (Retinal dystrophy): 30% is AR
- Hereditary motor and sensory neuropathy
Alport syndrome: Genes
X-linked: COL4A5
AR and AD: COL4A4 and COL4A3
Autosomal dominant polycystic kidney disease: Genes
PKD1, PKD2
Noonan syndrome: Genes
PTPN11 (50% & most common)
& others: MAP2K1 etc.
Retinitis pigmentosa/ Retinal dystrophies: Genes
30% are AR: Gene: RHO > Encodes: rhodopsin
Other genes are X-linked, AR, AD
Tuberous sclerosis: Genes
TSC1 and TSC2
Long QT syndrome (congenital): Genes
KCNQ1 & other genes
Genes coding for ion channel proteins (AR or AD)
Hypertrophic Obstructive Cardiomyopathy (HOCM): Genes
Genes coding for components of the sarcomere (AD)
Hereditary motor and sensory neuropathy (Charcot- Marie- Tooth disease): Genes
PMP22 (AD)
Other genes (AD, AR, or X-linked)
HNPCC (Hereditary non-polyposis colon cancer): Genes
AD + reduced penetrance:
DNA Mismatch repair genes >>>
The most common: MLH1, MSH2, MSH6
(= hMLH1, hMSH2, hMSH6)
& other genes (polygenic)
Hereditary breast and ovarian cancer: Genes
AD + reduced penetrance
BRCA1 & BRCA2
P53 & othe genes are less common
