Single gene disorders

Single gene disorders

DNA genetic code dictates amino acid identity and order

DNA sequence variation in a gene can change the protein produced by the gene

• allele - one of two or more alternative forms of a gene
• genotype - genetic constitution of an organism
• phenotype - observable properties of an organism produced by combination of genotype and environment
• mutation - alteration in DNA or chromosome sequence or structure, source of alleles and genetic variation

Mutations can be classified according to the type and effect of molecular change

• a single base substitution is called a point mutation
• these can have different effects depending on what they are, and where they are in a gene sequence
• mutations in non-coding regions of a gene can also have important effects

The consequences of point mutations in protein coding regions of genes

• nonsense mutation - produces premature stop codon
• missense mutation - single nucleotide is changed, resulting in a different codon and different amino acid

Frameshift mutations

• insertion or deletion can occur
• this causes a dramatic change in the protein sequence as all subsequent codons are affected

Mutations affecting metabolic pathways in humans (inborn errors of metabolism)

• homozygous/homozygote - a diploid organism having the same alleles at one or more genes
• heterozygous/heterozygote - a diploid organism having different alleles at one or more genes
• alleles can be dominant (phenotypically expressed in either the homozygous or heterozygous state) or recessive (phenotypically expressed only in the homozygous state)

Phenylketonuria (PKU)

• recessive mutation of phenylalanine hydroxylase gene
• homozygotes cannot metabolise Phe
• accumulating phenylalanine in the blood causes severe mental retardation, slow growth and early death
• affects 1 in 11,000 to 1 in 15,000
• routine test of newborn detects high blood Phe
• Low Phe diet can alleviate the effects of the mutation

Molecular basis of dominance/recessiveness

• tyrosinase catalyses the synthesis of melanin from tyrosine
• in oculocutaneous albinism the normal 'wild type' allele of the tyrosinase gene is dominant over the mutant allele
• heterozygotes with one normal allele make normal tyrosinase and can…