Human Pedigree Analysis

Family history important to identify genetically inherited diseases

Certain traits more common in closed off areas due to inbreeding

Human pedigree analysis used in genetic counselling for parents

Traits all start as mutation - some DNA mutates more than others (why diseases more prevalent than others)

3 primary patterns of inheritance - autosomal dominant, autosomal recessive, sex-linked

Inbreeding increases the chance of recessive disorders

Recessive - if neither parent has the characteric pheotype (disease) displayed by child, trait is recessive

Autosomal - gene is on one of autosome so male and female offspring equally likely to inherit trait

Trait can appear in offspring of related individuals (inbreeding)

Heterozygotes have normal phenotype so skips generations

Example - albinism

• Lack of melanin pigmentation
• Homozygous recessive individuals make no brown pigments = white to yellow skin/hair/eyes
• Heterozygous parents with normal pigmentation - 25% chance of alibino children
• Several muations cause albinism:
  • Lack of 1 or another enzyme along melanin-producing pathway
  • Inability of enzyme to enter pigment cells and convert amino acid tyrosine to melanin

Example - Phenylketonuria

• Sufferers lack ability to synthesize enyzme to convert to amino acid phenylalanine into tyrosine
• Homozygous individuals build up phenylalanine have abnormal breakdown products in urine and blood
• Breakdown products harmful to developing nervous systems = mental retardation
• PKU sufferers placed on a diet low in phenylalanine, enough for metabolic needs but not enough to cause build-up of harmful intermediates

Example - Sickle-cell Anaemia

• Autosomal recessive disease
• Causes single amino acid subsititution in beta chains of haemoglobin
• In low oxygen concentration, sickling of cells occurs
• Heterozygotes make enough 'good beta-chain haemglobin' so they do not suffer as long as oxygen concentrations are high

Example - Tay-Sachs Disease

• Degeneration of nervous system
• Symtons manifest after birth and children homozygous recessive rarely survive past 5 years old
• Sufferers lack ability to make enzyme N-acetyl-hexosaminidase, which breaks down GM2 ganglioside lipid
• Lipid accumulates in lysosomes in brain cells, killing brain cells

Trait that appears in successive generations due to dominant allele

Heterozygotes express mutant phenotype - 75% chance of passing on gene to progeny

Example - Huntingtons Disease

• Progressive destruction of brain cells
• Parent has disease, 50% of children will have it (unless parent is homozygous dominant)
• Disease usually not manifest until after 30 = difficult to eradicate from population

Example - Polydactyly

• Presence of 6th digit
• Modern - finger cut off at birth and individuals do not know they carry the trait

X-linked - trait preferentially seen in males (hemizygous), females are heterozygous carriers or homozygous

Males get mutant allele from mother

Affected males transmit mutant allele to daughters, but not sons

Most are recessive

Example - red-green colour blindness

• Colour percenption depends on 3 genes
• Red-green ones on X-chromosome, blue one on autosome

Example - Haemophilia

• Group of diseases in which blood does not clot normally
• Lack normal factor VII said to have haemophilia A