Genetic epidemiologic methods to screen for matrilineal inheritance in mitochondrial disorders.
We propose a method to screen for the matrilineal inheritance in mitochondrial disorders by comparing the risk of disease in a person whose mother is affected or whose maternal grandmother or aunt or uncle is affected to the risk of disease in a person whose father is affected or whose paternal grandmother or aunt or uncle is affected using a modification of the reconstructed cohort design. Sampling of pedigrees is accomplished 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 hazards model, Bonney's [(1986) Biometrics 42:611-625] model, and Liang's [(1991) Genet Epidemiol 8:329-338] model. Mitochondrial transmission can be distinguished from X-linked transmission by examining sex-specific patterns of disease expression in matrilineally transmitted diseases. To illustrate our epidemiologic method, we apply our screening method to pedigrees of two disorders which have been proposed to have a mitochondrial DNA component to their inheritance.
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Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA.
Flanders
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WD
Sherman
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SL
Go
R C
RC
Wallace
D C
DC
D001714:Bipolar Disorder / Q000453:epidemiology / Q000235:genetics; D015331:Cohort Studies; D004812:Epidemiologic Methods; D005111:Extrachromosomal Inheritance; D005260:Female; D030342:Genetic Diseases, Inborn / Q000453:epidemiology / Q000235:genetics*; D008040:Genetic Linkage; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000235:genetics*; D015418:Optic Atrophies, Hereditary / Q000453:epidemiology / Q000235:genetics; D018570:Risk Assessment; D014960:X Chromosome