Inheritance Patterns
It is important to understand the basic laws of inheritance to appreciate how conditionsare passed on in a family. An accurate family health history is a valuable tool toillustrate how conditions are passed down through generations.
A person has two copies of almost every gene, one copy from mom and one copy from dad.Scientists have studied human genes to learn how they normally work and how changes ingenes can change how they work. Some changes are very minor and do not affect the way agene works. These changes are often called single nucleotide polymorphisms (SNPs,pronounced “snips”) or gene variants. Other changes, called mutations,affect how a gene works and can lead to disease.
For some conditions, family members with the same mutation may not have the samesymptoms. For other conditions, individuals with different mutations can have similarcharacteristics. This is because gene expression is influenced by genes, as well as bythe environment.
Diseases caused by mutations in a single gene are usually inherited in a simple pattern,depending on the location of the gene and whether one or two normal copies of the geneare needed. This is often referred to as Mendelian inheritance because Gregor Mendelfirst observed these patterns in garden pea plants. Most single gene disorders are rare;but, in total, they affect millions of people in the United States.
Several basic modes of inheritance exist for single-gene disorders: autosomal dominant,autosomal recessive, X-linked dominant, and X-linked recessive. However, not all geneticconditions will follow these patterns, and other rare forms of inheritance such asmitochondrial inheritance exist. (See table at the end of this section.)
| Inheritance Pattern | Characteristics | Disease Examples |
|---|---|---|
| Autosomal Dominant | Each affected person usually has an affectedparent; occurs in every generation | Huntington’s disease,neurofibromatosis, achondroplasia, familial hypercholesterolemia |
| Autosomal Recessive | Both parents of an affected person arecarriers; not typically seen in every generation | Tay-Sachs disease, sickle cell anemia, cysticfibrosis, phenylketonuria (PKU) |
| X-linked Dominant | Females are more frequently affected becauseall daughters and no sons of an affected man will be affected; can haveaffected males and females in same generation if the mother isaffected | Hypophatemic rickets (vitamin Dresistantrickets), ornithine transcarbamylase deficiency |
| X-linked Recessive | Males are more frequently affected; affectedmales often present in each generation | Hemophilia A, duch*enne muscular dystrophy |
| Mitochondrial | Can affect both males and females, but onlypassed on by females because all mitochondria of all children come fromthe mother; can appear in every generation | Leber’s hereditary optic neuropathy,Kearns-Sayre syndrome |
Dominant mutations are expressed when only one copy of that mutation is present.Therefore, anyone who inherits one dominant disease mutation such as the mutation forHuntington’s disease will have that disease. Dominantly inherited geneticdiseases tend to occur in every generation of a family. Each affected person usually hasone affected parent. However, dominant mutations can also happen in an individual forthe first time, with no family history of the condition (spontaneous mutation).
Recessive mutations require two mutated copies for disease to develop. Recessive geneticdiseases are typically not seen in every generation of an affected family. The parentsof an affected person are generally carriers: unaffected people who have a copy of amutated gene. If both parents are carriers of the same mutated gene and both pass it tothe child, the child will be affected.
Inheritance patterns differ for genes on sex chromosomes (chromosomes X and Y) comparedto genes located on autosomes, non-sex chromosomes (chromosomes numbers 1-22). This isdue to the fact that, in general, females carry two X chromosomes (XX), while malescarry one X and one Y chromosome (XY). Therefore, females carry two copies of eachX-linked gene, but males carry only one copy each of X-linked and Y-linked genes.Females carry no copies of Y-linked genes.
Diseases caused by mutated genes located on the X chromosome can be inherited in either adominant or recessive manner. Since males only have one X chromosome, any mutated geneon the X chromosome, dominant or recessive, will result in disease. Because females havetwo copies of X-linked genes, they will not be affected by inheriting of a singlerecessive mutation on an X-linked gene. For X-linked recessive diseases to occur infemales, both copies of the gene must be mutated. Families with an X-linked recessivedisorder often have affected males, but rarely affected females, in each generation.
For X-linked dominant diseases, however, a mutation in one copy of an X-linked gene willresult in disease for both males and females. Families with an X-linked dominantdisorder often have both affected males and affected females in each generation.
A striking characteristic of X-linked inheritance is that fathers cannot pass X-linkedtraits to their sons; fathers only pass X chromosomes to their daughters and Ychromosomes to their sons. In contrast, mothers pass X-linked genes to both sons anddaughters.
