Overview of Mendelian inheritance
- Benjamin A Raby, MD, MPH
Benjamin A Raby, MD, MPH
- Section Editor — Genetics
- Associate Professor of Medicine
- Harvard Medical School
Most clinical disorders with a genetic basis result from complex interactions between multiple genes (multigenic) and environmental factors, termed multifactorial inheritance. Monogenic disorders (genetic disorders caused by mutations in only one gene) are relatively rare and are often first recognized clinically by their predictable patterns of inheritance in families.
Predictable, single gene patterns of inheritance were first observed in plants by an Augustinian monk and botanist, Gregor Mendel (Mendelian inheritance) . Based on observations from a large series of cross-breeding experiments of plants with varying flowering characteristics, Mendel proposed his Laws of Inheritance. These laws were soon translated to the clinical setting by Sir Archibald Garrod and launched the study of medical genetics .
The explosion in the field of medical genetics, following sequencing of the human genome and the more recent development of next-generation sequencing technologies, has led to identification of numerous specific genes associated with human genetic disorders. Whereas in 1990 the genetic basis was known for fewer than 2 percent of Mendelian diseases, in 2011 the molecular basis is understood for nearly 40 percent of these conditions, giving rise to more accurate diagnostic testing and the promise of novel treatments to be developed . With the advent of whole genome and whole exome resequencing methods, it is likely that the majority of variants underlying the remaining monogenic diseases will be mapped within the next few years.
This topic will review Mendel's Laws of Inheritance and link these laws to our modern understanding of molecular genetics. Patterns of monogenic inheritance and means of recognizing them in the clinical setting will be described. A brief overview of the major causes of non-Mendelian inheritance is presented. A discussion of genetic variation and a glossary of terms related to genetics are presented separately. (See "Overview of genetic variation" and "Genetics: glossary of terms".)
The following terminology is used in describing Mendelian traits and Mendelian inheritance patterns:
- Mendel G. Versuche über Pflanzen-Hybriden (Experiments in Plant Hybridization). Ver Brünn 1866; 4:3.
- Garrod AE. The incidence of alkaptonuria: a study in chemical individuality. Lancet 1902; 160:1616.
- Feero WG, Green ED. Genomics education for health care professionals in the 21st century. JAMA 2011; 306:989.
- Giles RE, Blanc H, Cann HM, Wallace DC. Maternal inheritance of human mitochondrial DNA. Proc Natl Acad Sci U S A 1980; 77:6715.
- CAN C, NIGOGOSYAN G. Acquired toxic porphyria cutanea tarda due to hexachlorobenzene. Report of 348 cases caused by this fungicide. JAMA 1963; 183:88.
- MENDEL'S LAWS OF INHERITANCE
- Law of segregation
- Law of independent assortment
- Law of dominance
- MOLECULAR BASIS OF MENDEL'S LAWS
- MENDELIAN INHERITANCE PATTERNS
- Autosomal dominant inheritance
- Autosomal recessive inheritance
- Compound heterozygosity
- Sex-linked inheritance
- CAUSES OF NON-MENDELIAN INHERITANCE AND EFFECTS THAT CONFOUND RECOGNITION OF MENDELIAN INHERITANCE
- Incomplete penetrance
- Sex-limited expression
- Parent-of-origin effects
- Multigenic disorders and genetic heterogeneity
- Mitochondrial inheritance
- Environmental effects