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Summary of Genetic Diseases

Disease

Mutation

Position

Causes

Inheritence

Symptoms

Polydactyly

 

 

 

Autosomal dominant

 

Huntington’s

CAG expansion

Exon 1

Direct neurotoxic effect?

Autosomal dominant, progressive symphtoms during life

Clumsy, forgetful, chorea, dimentia

Cystic fibrosis

 

 

 

Autosomal recessive

 

Fragile X

CGG expansion

5’UTR of FMR gene, Xq27.3

Promotes genomic methylation, reduction in transcription

X-linked; 20% men not affected, 30-50% women affected

Mental retardation, etc.

Duchenne Muscular Dystrophy

Disrupting translocation (loss)

Between 5’ and 3’ UTR

 

X-linked recessive

 

Myotonic Dystrophy

Expansion

3’UTR,

 

(possiblyà)

disturbs intracellular movement of mRNA and thus location

 

 

Friedrich Ataxia

Expansion of intron

5’ end of gene

Disturbs splicing: defective short protein

 

Odd gait, neurological, cardiovascular

AML retinoic acid sensitive protein

Translocation generates novel (gain)

Between 5’ and 3’ UTR

 

 

 

Prader-Willi

15q deletion

Chromosome 15, long arm, PATERNAL chromosome

MATERNAL HEAVILY METHYLATED SO DIFFERS FROM ß

Also if MATERNAL disomy plus 15q deletion

Epillepsy, mental retardation, physical disabilities, obesity

Angelman

15q deletion

Chromosome 15, long arm, MATERNAL chromosome

MATERNAL HEAVILY METHYLATED SO DIFFERS FROM Ý

Also if PATERNAL disomy plus 15q deletion

Happy moon-shaped faces, small feet, sophisticated spatial abilities but feeding probs, obesity

Breast cancer

Multiple

BRCA1, 2, p53

succeptibility

 

Bowel cancer

Many e.g. à

Mismatch repair genes

Non-polyposis coli

 

IDDM

Multiple

HLA regions of 6p21

Sifferent combinations confer Succeptibility or resistance

 

Atherosclero sis

Multiple

LDL receptor, angiotensin, ApoLP A, B

LDL receptor: familial hypercholesterolaemia

Prognosis of heart disease by age of 40-50

Alzheimers disease

Multiple

Apolipoprotein E

E4 allele highest risk

 

 

 

Summary:

MUTATION TYPE                                              EXAMPLE

Affects transcription due to methylation                FRAXA, Prader-Willi, Angelmans

Splicing prevented                                              Friedrich’s Ataxia

Affects alternative splice proportions                    Frontotemporal dementia

Affects half life (poly A)                                                   Cystic Fibrosis

Affects translocation                                           MD

Affects folding

Affects active site                                               Ras mutations (GTP site)

 

Aneuploidy

Genotype

Phenotype

Sex chromasomes:

Sry determines male, otherwise female

Turner’s syndrome

45, X, FEMALE

Short, shield chest, slight learning difficulties, infertile

Kleinfelter’s syndrome

47, XXY, MALE

Female fat distribution, infertile, gynacomastia (breasts)

 

47, XYY, MALE

Tall, occasional educational difficulties

 

47, XXX, FEMALE

Autosomal:

Acrocentric chromasomes (large q arm) in Robertsonian (whole chromosome) translocations 13, 14, 15, 21, 22. Only three viable, others abort, unless significant mosaicism

Down syndrome

Trisomy 21

Epicanthric folds, mentally retarded, heart defects, varying degrees of severity

Edward’s syndrome

Trisomy 18

Very poorly, clenched fist with overlapping fingers

Patau syndrome

Trisomy 13

Midline defects, CNS/brain defects, polydactyly, 90% die in first year

Triploidy

69XXY

Diploid egg

or double fertilisation

occasionally survive to birth, not long after

Triploidy

69XYY

Triploidy

69XXX