GENETIC EPIDEMIOLOGIC METHODS TO SCREEN FOR MATRILINEAL INHERITANCE IN MITOCHONDRIAL DISORDERS

We propose a method to screen for the matrilineal inheritance in mitoc hondrial disorders by comparing the risk of disease in a person whose mother is affected or whose maternal grandmother or aunt or uncle is a ffected to the risk of disease in a person whose father is affected or whose paternal grandmother or aunt or uncle is affected using a modif ication of the reconstructed cohort design. Sampling of pedigrees is a ccomplished via probands and must not be influenced by family history. The cohort of the proband's offspring, and offspring of the proband's siblings, can be analyzed using survival analysis, Cox proportional h azards model, Bonney's [(1986) Biometrics 42:611-625] model, and Liang 's [(1991) Genet Epidemiol 8:329-338] model. Mitochondrial transmissio n can be distinguished from X-linked transmission by examining sex-spe cific patterns of disease expression in matrilineally transmitted dise ases. To illustrate our epidemiologic method, we apply our screening m ethod to pedigrees of two disorders which have been proposed to have a mitochondrial DNA component to their inheritance. (C) 1996 Wiley-Liss , Inc.