Non-Mendelian Genetics

Non-Mendelian Genetics

Genetic Imprinting

·        = Differential expression of genetic material depending on whether it has been inherited from male or female parent

·        Þ Parent of origin of mutation matters for many genes

·        Affected genes are usually highly conserved (ie the same genes appear in mice and humans – conserved through evolution)

·        Myotonic dystrophy:

o  Autosomal dominant

o  Progressive weakness from 3^rd decade

o  Unstable triplet repeat on 19 (upper limit of normal is 50 repeats)

o  Most unstable when its from mum (ie parental imprinting) 

o  As number of repeats increases goes from normal ® premutation carrier ® affected

·        Fragile X Syndrome:

o  Abnormal if triplet repeat > 200

o  Only expands when passed from mother to son, not to daughter

·        Huntington‟s:

o  Unstable triplet repeat syndrome 

o  If father passes it on then greater risk of ­ number of repeats

o  See Topic: Dementia

Uniparental Disomy (UPD)

·        = Presence of a cell line containing 2 chromosomes both inherited from only one parent

·        Has been demonstrated in cystic fibrosis, haemophilia (ie got both mutated genes from the one parent)

·        Prader-Willi Syndrome:

o  Floppy baby, low birth weight, retarded, ­­appetite ® obesity, short statue

o   Caused by deletion on father‟s Chr 15, or have both normal Chr 15 from mum (ie no 15 from dad)

o  Angelman Syndrome caused by maternal deletion of the same chromosome ® low birth weight, unusual cry, stiff legged gait, tremour and seizures

Mitochondrial Disorder

·        Mitochondria:

o  Generate ATP for energy using the respiratory chain

o  Contain their own DNA: circular double stranded DNA

o  All come from mother

o  Have higher mutation rate

·        Heteroplasmic: up to 200 mitochondria per cell, up to 20 different DNAs per cell

·        Usually involves all tissues, very variable expression

·        Difficult to test for and hard to treat