1) Inherited dysfunction due to somatic change Definition: Sporadic mutations causing changes in the bodys cells.

These mutations can be passed on in a family. Example: Queen Victoria had a spontaneous mutation for hemophilia and it was passed on throughout the royal family. 2) Haploinsufficiency Definition: Haploinsufficiency is the situation in which a disease is caused by the loss of half of the normal activity of a protein. Example: Williams syndrome, a neurodevelopmental disorder caused by haploinsufficiency 3) Dominant negative Definition: A situation in which an abnormal protein is produced that leads to abnormal phenotypes due to interference with the function of the product of the normal allele. Example: Marfan syndrome- affected FBN1 gene causes production of abnormal fibrillin-1 which in turn, affects the connective tissue supporting the bodys joints and organs. 4) Dominant gain of function Definition: A mutation in which dominance is led by the changing of the expression pattern. Example: A dominant gain of function mutation in Hsp104p promotes survival after extreme stress. 5) Microdeletion Definition: Situation in which there is a deletion of multiple genes at closely linked loci or by environmental exposures shared among family members. Example: Prader-Willi syndrome, which is caused by the microdeletion of 15q11-13. 6) Age of onset Definition: Period of time at which an individual experiences symptoms of a disease. Example: The age of onset for sickle cell anemia is during childhood, within the first year the individual is born. 7) Locus heterogeneity Definition: Mutations at different loci. Example: In retinitis pigmentosa, occurs in autosomal dominant, autosomal recessive, and Xlinked forms. 8) Allelic heterogeneity

Definition: Mutations at the same locus. Example: Mutations in the RET gene can cause dominantly inherited failure of development of colonic ganglia, leading to Hirschsprung disease. 9) Loss of heterozygosity Definition: At a specific locus heterozygous for a deleterious mutant allele and a normal allele, a mutational even within the normal allele causes the cell to be either hemizygous (one deleterious allele and one deleted allele) or homozygous for the deleterious allele. Example: Retinoblastoma 10) Inbreeding Definition: Breeding of related individuals who are closely related genetically. Example: Inbreeding is common in Japan, southern India, and the Middle East. 11) Consanguinity Definition: A mutant allele originating from the parents being carriers due to having a single common ancestor. Example: Consanguinity is common in Japan, southern India, and the Middle East. 12) Sex influence Definition: Phenotypes that are expressed in both sexes but with different frequencies. Example: Hemochromatosis is more common in males.