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Glossary of Genetic Terms

Introduction to Genetics

How We Find Genes

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How We Find Genes

The Center for Human Genetics uses the following strategies to identify genes that contribute to disorders:

Genome Screen and Linkage Analysis

Genome screens and linkage analysis have been very successful in discovering the genes that cause many genetic disorders. Advances in laboratory and computer technology have made this approach possible for complex disorders like neural tube defects. The genome comprises all of a human’s genetic material. A genomic screen consists of DNA laboratory studies and a statistical analysis called linkage analysis. Linkage analysis is the first step towards finding a gene.

Looking for the genes that cause a genetic disorder is similar to locating someone’s house without knowing the exact address. By narrowing down the area you are searching in (from state to city to street), eventually you can find the address of a particular person. Just as gas stations or restaurants can be used as landmarks when locating a friend’s house, scientists use markers to find a gene. The instructions encoded in genes are written in a special genetic alphabet consisting of four letters: – A, T, C, and G (called nucleotide bases). These bases are the critical chemicals from which DNA is made. The sequence (order in which these letters occur) tells the body how to make certain proteins. Markers are the small sequences of DNA along the chromosomes that may differ slightly from individual to individual. These differences (called polymorphisms) do not usually affect a person’s health, but can be easily identified and used to look for genes.

Linkage analysis is performed by testing many different markers on all the chromosomes, trying to find markers that are consistently found in family members who have the disorder, but are not found in family members without the disorder. These markers are used as landmarks to identify exactly which chromosome a gene causing a disorder is located on. Certain statistical methods tell scientists how close these landmarks are to a gene. If a marker is believed to lie very close to a gene, then the marker is “linked” to the gene. This is why we call this DNA analysis “linkage analysis.”

Candidate Gene Analysis

Candidate genes help explain a disorder because of their location or function in the body. Candidate gene analysis for a disorder involves studying the potential candidate gene in individuals with the disorder to see if the gene has a genetic change (mutation) that is not seen in the genes of individuals who do not have the disorder. If genetic changes in candidate genes are identified, then it is possible the candidate gene contributes to the development of the disorder.

A Combined Strategy is Most Successful

Our laboratory strategy is to study candidate genes in families in which only one individual has the disorder. We then combine the study of candidate genes with linkage analysis using DNA samples from families with more than one individual with the disorder. Once an area, such as a particular piece of one chromosome, is identified as being linked through the genomic screen, then we study candidate genes located on that particular piece of the chromosome. This combined strategy helps narrow the potential candidate genes. Computer databases, developed in part by the Human Genome Project, identify which genes are located on a particular piece of a chromosome. We then study potential candidate genes to determine if they are truly related to the disorder. In other words, the results of the genomic screen and linkage analysis give us the street on which an individual’s house is located. Candidate gene analysis is like knocking on the door of a house on that street looking for a friend. Our laboratory has been successful in discovering the genes that contribute to the development of complex disorders. We are confident that this combined strategy will increase the chances of discovering which genes are involved in the development of disorders.

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