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Collection of Clinical and Epidemiological Data for Genetic Linkage and Association Studies

Lindsay Farrer¹, Mark Logue¹

¹Boston University School of Medicine, Boston, Massachusetts

Publication Name:

Current Protocols in Human Genetics

Unit Number:

Unit 1.1

DOI:

10.1002/0471142905.hg0101s72

Online Posting Date:

January, 2012

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Abstract

Modern gene‐mapping can include linkage studies, which correlate the presence of disease to broad genomic regions in either small or large family units, and association studies, which can narrow the location of a disease‐predisposing trait to a single gene using either case‐control or family data. This unit provides an overview of key concepts and presents guidelines for collecting diagnostic, epidemiological, and genealogical data from potential study participants. The commentary discusses the use of publicly available data from online resources, methods for evaluating evidence of genetic versus environmental influences in a disease or disease‐related endophenotype, and use of e‐forms to capture data electronically. Curr. Protoc. Hum. Genet. 72:1.1.1‐1.1.20 © 2012 by John Wiley & Sons, Inc.

Keywords: genetics and genomics; genetic linkage analysis; genetic association analysis

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Introduction
Key Concepts
Strategic Approach: Collecting Data for Linkage and Association Studies
Commentary
Literature Cited
Figures
Tables

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Figures

Figure 1.1.1

Pedigree showing incomplete penetrance for autosomal dominant disease. Males and females are designated by squares and circles, respectively. A dark symbol indicates that person is affected. The arrow points to proband through which pedigree was ascertained. Father of proband is nonpenetrant; he is unaffected but must possess the disease allele.

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Figure 1.1.2

Distribution of age at onset in Huntington disease (n = 610). Percentage of total cases (relative frequency) is plotted against age at which they occur. From Farrer and Conneally (1985).

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Figure 1.1.3

Pedigree of family with Huntington disease showing age‐dependent penetrance. Few persons in youngest generation are affected because most HD gene carriers among them are not old enough to manifest symptoms. A half‐shaded symbol indicates the person is affected. A slash through the symbol indicates that the person is deceased. Numerals within symbols represent multiple unaffected individuals of the same sex; numerals below symbols represent age at onset (for affected individuals) or age at last exam (for unaffected individuals).

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Figure 1.1.4

Flow chart for collecting diagnostic and epidemiological data for linkage studies (as described in Strategic Approach).

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Figure 1.1.5

Sample patient history form.

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Figure 1.1.6

Sample design for collecting, transmitting, storing, and retrieving information using an electronic data management system. Questionnaire information is collected with some error checking and validation using electronic forms installed on laptop computers (see text for details). Data are submitted electronically via the Internet to a database server and archived into a permanent database. These data can be accessed by personnel in the data coordinating center for further verification, generating report summaries, and analysis purposes. This scheme also permits staff involved in data collection to view individual data and reports using a Web browser.

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Literature Cited

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Key References
	Khoury et al., 1993. See above.
A thorough introduction to genetic approaches to familial aggregation.
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Contains excellent description of medical genetics concepts.
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A detailed overview of the use of electronic medical records in genetic studies of human disease.
Internet Resources
	http://www.omim.org/
URL for Online Mendelian Inheritance in Man (OMIM). McKisick‐Nathans Institute for Genetic Medicine, Johns Hopkins University (Baltimore, Md.) and National Center for Biotechnology Information, National Library of Medicine (Bethesda, Md.).
	http://www.ncbi.nlm.nih.gov/gap
URL for data base of Genotypes and Phenotypes (dbGaP),National Center for Biotechnology Information, National Library of Medicine (Bethesda, Md.).