GDC inheritance

autosomal dominant inheritance

1. it will be present in each generation

2. if it leaves 1 lineage it will never return again

ex: achondroplasia, huntington’s, neurofibromatosis

autosomal recessive

1. usually no familly history

2. if a child is affected they most likely have an affected sibling

3. risk increases in consanguinous relationships

ex: sickle cell disease, tay sachs, cystic fibrosis

homozygous lethals

1. the homozygous genotype expresses a more sever phenotype than heterozygous

ex: achondroplasia and sickle cell disease

semi-dominance

1. phenotype is intermediate between homozygous genotypes

ex: familial hypercholesterolinaemia

• homozygous → death in childhood

• heterozygous → death in young adulthood

co-dominance

1. phenotype of multiple genes can be distinguished

ex: ABO

• H antigen is processed by glycosyl-transferace coded by ABO genes

• A → N-acetylgalactosamine

• B → D-galactose

• C → nothing

silent allele

allele that doesn’t produce a detectable gene product

ex: O blood group of, adenosine deaminase

1. linked to severe combined immunodeficiency and haemolytic anaemia

epistasis

phenotype of a gene is masked by another gene involved in the same pathway

ex:

• bombay phenotype → gene coding of H antigen is required to express AB → defects causes blood group O even if u have genotype for A or B

• albinism → gene coding for melanine is defective → genes for hair and skin colour are unable to express

pleiotropy

gene is involved in several tissue and organ types → symptoms manifest differently in different individuals

ex:

1. sickle cell

2. autism

3. schizophrenia

4. albinism

5. phenylketonuria

6. marfan’s syndrome (fibrillin 1 gene)

genetic heterogeneity

1 condition can be caused by defects in several genes

ex: tuberous sclerosis

1. chromosome 9 TSC1 → HAMARTIN

2. chromosome 6 TSC2 _> TUBERIN

Variable expressivity

condition can present in many different ways

ex: polydactyly

incomplete penetrance

extremely low expressivity causing some carriers to not show symptoms even if parents or children do

ex: BRCA1 and 2 gene in breast cancer

phenocopies

condition caused by environmental factors mimics that of a genetic condition

ex: thalidomide and phocomelia

anticipation

earlier onset of disease with increased severity due to expansion of trinucleotide repeat

ex:

1. huntington’s → CAG repeat

2. fragile X syndrome

3. mytonic dystrophy

incomplete ascertainment

if a genetic condition is recessive there is no familly history causing observation to be biased towards people with affected children

NM → mitochondral inheritance

1. only inherited from the mother → all children of affected mother have disease no children from affected father has the disease

ex:

1. myoclonic epilepsy with ragged red fibres (MERF)

2. mitochondral encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS)

3. LEBER’S HEREDITARY OPTIC NEUROPATHY

what complicated mitochondral inheritance

1. nucleus incoded mitochondrial genes

2. somatic mutations/changes

3. heteroplasmy

NM→ uniparental disomy

children inherites both copies of a chromosome from 1 parent

ex: cystic fibrosis

NM → gene linkage

genes that are very close to each other on the chromosome are inherited together

x-linked dominant conditions

affected males → all daughters affected, no sons affected

1. incontinentia pigmenti → IP2 gene defect

2. congenital generalised hypertrichosis

X-linked recessive conditions

usually only males are affected and dont pass down the condition

ex:

1. duchenne muscular dystrophy

2. haemophilia A (8) and B (9)

3. G-6-P dehydrogenase deficiency

4. colour blindness

how are x-linked recessive conditions expressed in girls

1. symptoms occur due to inactivation of healthy copy → fabry disease

2. disease is expressed but with milder symptoms

3. some genes escape inactivation

4. cells where non mutated gene is active have diffusible gene products → haemophilia A

5. there is preferential inactivation of the defective copy

imprinting

false impression of X-linkage due to epigenetic inactivation of allele

ex: CHROMOSOME 15 gene deletion

1. prader-willi: paternal copy of PW5 gene is mutated whilst maternal copy is silenced → developmental retardation and increased apetite

2. angelman: maternal copy of UBE3A gene is mutated whilst paternal copy is silenced → developmental retardation