The basic laws of inheritance are important in understanding patterns of diseasetransmission. The inheritance patterns of single gene diseases are often referred to asMendelian since Gregor Mendel first observed the different patterns of gene segregation forselected traits in garden peas and was able to determine probabilities of recurrence of atrait for subsequent generations. If a family is affected by a disease, an accurate familyhistory will be important to establish a pattern of transmission. In addition, a familyhistory can even help to exclude genetic diseases, particularly for common diseases wherebehavior and environment play strong roles.
Most genes have one or more versions due to mutations or polymorphisms referred to asalleles. Individuals may carry a ‘normal’ allele and/or a‘disease’ or ‘rare’ allele depending on the impact of themutation/polymorphism (e.g., disease or neutral) and the population frequency of the allele.Single-gene diseases are usually inherited in one of several patterns depending on thelocation of the gene and whether one or two normal copies of the gene are needed for thedisease phenotype to manifest.
The expression of the mutated allele with respect to the normal allele can be characterizedas dominant, co-dominant, or recessive. There are five basic modes of inheritance forsingle-gene diseases: autosomal dominant, autosomal recessive, X-linked dominant, X-linkedrecessive, and mitochondrial.
Genetic heterogeneity is a common phenomenon with both single-gene diseases and complexmulti-factorial diseases. It should not be surprising that multiple affected family membersmay experience different levels of disease severity and outcomes. This effect may be due toother genes influencing the disease phenotype or different mutations in the same generesulting in similar, but not identical phenotypes. Some excellent resources for informationabout single-gene diseases is the Online Mendelian Inheritance in Man (OMIM; http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM) andGeneTests/GeneClinics (http://www.genetests.org).
Patterns of Inheritance
Autosomal Dominant
Each affected person has an affected parent
Occurs in every generation
Autosomal Recessive
Both parents of an affected person are carriers
See AlsoAzalea PinkNot typically seen in every generation
X-linked Dominant
Females more frequently affected
Can have affected males and females in same generation
X-linked Recessive
Males more frequently affected
Affected males often present in each generation
Mitochondrial
Can affect both males and females, but only passed on by females
Can appear in every generation
| Inheritance Pattern | Disease Examples |
|---|---|
| Autosomal Dominant | Huntington’s disease,neurofibromatosis, achondroplasia, familial hypercholesterolemia |
| Autosomal Recessive | Tay-sachs disease, sickle cell anemia, cysticfibrosis, phenylketonuria (PKU) |
| X-linked Dominant | Hypophatemic rickets (vitamin D-resistantrickets), ornithine transcarbamylase deficiency |
| X-linked Recessive | Hemophilia A, duch*enne muscular dystrophy |
| Mitochondrial | Leber’s hereditary optic neuropathy,Kearns-Sayre syndrome |
