Part 2: The Genetic Basis of Disease

Part 2: The Genetic Basis of Disease • Glossary of terms • Dominant and recessive alleles in human disease • Complex genetics: polygenic and multiple allelic traits • Levels of dominance: co-dominance and incomplete dominance • Sex-linked disorders

A Glossary of Terms Used in Genetics • Gene: a unit of inheritance • Allele: alternative forms of a gene (for example, dominant and recessive) • Genotype: the genetic constitution of an organism (that is, its content of alleles) • Heterozygous: possessing two different alleles for a particular gene • Homozygous: possessing two identical alleles for a particular gene • Phenotype: the characteristics of an organism (to a large extent, a consequence of its genotype)

Father AA Mother aa Father Aa Mother Aa Sperm cell A Egg cell a Sperm cell A or a Egg cell A or a Zygote Aa Zygote AA, Aa or aa Inheritance: The Principle of Segregation

Interpreting Inheritance: the Punnett Square Simple dominant/recessive relationship: Aa x Aa Inheritance of genetic disease: AAD x AAD

Huntington’s Disease: an Autosomal Dominant Disorder • Neurodegenerative condition affecting 1/10,000 Caucasians, with symptoms typically beginning in early middle age • Caused by a trinucleotide repeat in a gene on chromosome 4 • Heterozygote (AAD) will develop the disease AAD x AA

Cystic Fibrosis: an Autosomal Recessive Disorder • 1/20 US Caucasians is a carrier (AAD); 1/2,500 is affected (ADAD) • Characterized by a build up of mucus in the lungs, due to defective chloride transport into lungs • Caused by a mutant allele of a gene on chromosome 7 AAD x AAD

Pedigree Charts: Showing Inheritance from One Generation to the Next Autosomal dominant disorder Autosomal recessive disorder

Polygenic Traits • Many phenotypes are determined by more than one gene e.g. skin colour, height, weight • A number of human disorders are influenced by more than one gene e.g. high blood pressure, allergies, behavioural patterns • Alleles of certain genes may predispose an individual to a disorder, but they do not necessarily cause the disorder • Environmental effects can complicate the genetic analysis of polygenic disorders

Multiple Allelic Traits ABO Blood Types • A: A antigen is expressed on red blood cells • B: B antigen is expressed on red blood cells • O: neither antigen is expressed

Levels of Dominance • Co-dominance • alleles are equally expressed in the heterozygote(e.g. AB in ABO blood typing) • Incomplete dominance • heterozygote displays an intermediate phenotype between the two homozygotes

Incomplete Dominance: Sickle Cell Disease • Caused by a mutation in both alleles of a globin gene (genotypically HbSHbS) • Red blood cells are elongated (not round) and clog blood vessels • Heterozygote (genotypically HbHbS) is phenotypically normal but may develop sickle cells when deprived of oxygen (carries the sickle cell trait) • 50% or more of the population in malaria-infested regions of Africa may carry the sickle cell trait

Sex-Linked Disorders • More males than females are affected • Affected son can have parents who are normal • The disorder often skips a generation XY x XBXb

Queen Victoria Prince Albert 8 other children Alice Louis IV Nicholas II Alexandra Alexis 4 daughters Sex-Linked Haemophilia (Haemophilia B)

Summary of Part 2 • Genes can occur as dominant or recessive alleles: there may be more than two alleles (multiple alleles) for a given gene • Many phenotypes, including some human disorders, are polygenic (influenced by more than one gene) • Dominant alleles may show co-dominance or incomplete dominance • Some phenotypes and disorders (e.g. haemophilia B) are sex-linked

Part 2: The Genetic Basis of Disease