Genes and Diseases
Genetic disorders are extremely common, with an estimated lifetime frequency of 67%; this includes not only “classic” genetic disorders but also cancer and cardiovascular diseases with complex multigenic contributions.If one counts all conceptuses, the actual frequency is probably greater, since 50% of early spontaneous abortions have a demonstrable chromosomal abnormality; the vast majority of genetic disorders do not result in a viable birth. Even so, approximately 1% of new-borns have a gross chromosomal abnormality, and 5% of individuals younger than 25 years have a serious disease with a significant genetic component. Causes of genetic disorders can be classified as follows:
- Mutations in single genes: These are usually highly penetrant (i.e., mutation typically results in disease) and follow classical Mendelian inheritance patterns.
- Chromosomal (cytogenetic) disorders: These arise from structural (e.g., breaks) or numerical alterations in chromosomes; they are usually highly penetrant.
- Multigenic disorders: These are the most common cause of genetic disorders and are caused by the complex interactions of multiple variant (not mutant) forms of genes (polymorphisms) and environmental factors. Independently, each polymorphism has only a small effect and is of low penetrance. Progress in genomics and bioinformatics has allowed genome-wide association studies (GWAS) to begin to identify the various genetic risk factors and contributions.