A handout for this lecture is available here.

MENDELIAN:

• mutation in single gene
• necessary and sufficient for phenotypes
• simple patterns of inheritance

• variations or distortions of mendelian inheritance (pseudo non-mendelian)
• genuine non-mendelian

INTERFAMILIAL:
Allelic variation, eg: beta⁰ vs beta⁺ thalassaemia; Duchenne/Becker Muscular Dystrophy (Becker is a milder form - does not disrupt the reading frame).

INTRAFAMILIAL:
Modifier genes (eg: HPFH in beta-thalassaemia - hereditory persistence of foetal haemoglobin)
Anticipation (expanded triplet repeat), eg: Huntington’s, Fragile X - the bigger the expansion, the greater the clinical severity.

Eg: myotonic dystrophy:
Generation 1 - bilateral cataracts
Generation 2 - facial weakness, ptosis, myotonia, cataracts
Generation 3 - severe, congenital hypotonia

DMD (Xp21) - see pictures 3 and 4 on the handout

Mosaic - an individual with two genetically different cell lines which result from a post-zygotic mutation.

Germline mosaicism - presence of a subset of germ cells carrying a mutation.
Somatic mosaicism - a subset of somatic cells carries mutation.

• differential expression of the maternal or paternal allele of a gene
• occurs in a limited number of autosomal genes

• mouse embryos with 2n paternal or maternal genomes are non-viable
• phenotype of human triploid abortus dependent on paternal origin of extra genome
• parental origin of certain chromosomal deletions determines the clinical phenotype (eg: Prader-Willi syndrome -vs- Angelman syndrome).

• transcriptional control involving differences in DNA methylation.
• PRADER-WILLI - short and obese - paternally derived chromosome deletion
• ANGELMAN - epileptic, ataxic gate, smile a lot - maternally derived chromosome deletion
• both above conditions are produced by a deletion of 15q11-q13 - but very different phenotypes.

See picture 2 on the handout (uniparental disomy)

Inflammatory bowel disease - hereditary? People in the same family are often affected - looking at pedigrees shows you that they don’t look normal:

• no clear mendelian mode of inheritance of clinical phenotype is discernible - familial clustering is observed.
• explain by assuming that the inheritance and expression of the phenotype is determined by multiple genes at different loci, each exerting an additive effect.
• each gene confers a moderately increased susceptibility to the disorder - eg: Crohn’s disease (eg: chromosomes 1, 12, 16).

See picture 5 on the handout - Mitochondrial inheritance
The male has not transmitted it to his children - on females => mutations occurring in mitochondrial DNA - supplied to the foetus from the ovum and not the sperm.

See picture 6 on the handout - Mitochondrial genome
Codes for about 37 genes, many of which are for oxidative phosphorylation enzymes.