It Runs in the Family

It Runs in the Family
Reported by
Catherine Zandonella

Posted January 12, 2010


The vast majority of genetic disorders are caused by a combination of genes, often set off by environmental influences. The first step in finding genetic causes for such diseases is to discover which chromosomal loci are involved. One strategy is to look for loci that are common among affected individuals in families, and then to figure out whether any of those loci contain genes that cause the disease. Since the exact genes are not known, geneticists use genetic markers, regions of the chromosome whose positions are known. If a marker locus is in close proximity to a disease locus, then the two may be inherited together, so marker genotypes are often associated with disease status.

With the human genome sequenced, we now know the locations of about 10 million genetic variations, known as single-nucleotide polymorphisms (SNPs), that can serve as markers. The genotypes of 500,000 of the more common SNPs can be evaluated simultaneously on a single gene microarray chip to search rapidly for correlations between genetic markers and disease status. At a June 22, 2006, meeting, speakers described advances in microarray-based genetic technologies and genome-wide association analyses.

Use the tabs above to find a meeting report and multimedia from this event.

Web Sites

Affymetrix produces gene microarrays that contain high-density arrays of peptides and oligonucleotides on small glass substrates. This site contains interviews with scientists that use the microarrays in genetic research.

The Human Genome
This website aims to provide key information about the human genome: the science, its role in health and medicine, and the broader social impact of unraveling its mysteries. The site is produced by the Wellcome Trust, the independent research funding charity.

National Human Genome Research Institute (NHGRI)
The NHGRI supports the development of resources and technology that will accelerate research on the structure and function of the human genome and its role in health and disease.

Primer on Molecular Genetics
This publication and the booklet "To Know Ourselves" from the Human Genome Project can be downloaded or read online. They cover what is known so far about the human genome, how the genome is sequenced, and ethical issues.


Haines, J. L. & M. A. Pericak-Vance, Eds. 2006. Genetic Analysis of Complex Disease. Wiley-Liss, Hoboken, NJ.

Ott, J. 1999. Analysis of Human Genetic Linkage. The Johns Hopkins University Press, Baltimore, MD.

Thomas, D. C. 2004. Statistical Methods in Genetic Epidemiology. Oxford University Press USA, New York.

Journal Articles

When the Chips Are Up: High-throughput Genetic and Genomic Studies of Neuropsychiatric Disease

Middleton, F. A., C. N. Pato, K. L. Gentile, et al. 2005. Gene expression analysis of peripheral blood leukocytes from discordant sib-pairs with schizophrenia and bipolar disorder reveals points of convergence between genetic and functional genomic approaches. Am. J. Med. Genet. B Neuropsychiatr. Genet. 136: 12-25.

Middleton, F. A., M. T. Pato, K. L. Gentile, et al. 2004. Genome wide linkage analysis of bipolar subjects using high density single nucleotide polymorphisms (SNP) genotyping arrays: a comparison with microsatellite markers and finding of significant linkage to chromosome 6q22. Am. J. Hum. Genet. 74: 886-897.

Middleton, F. A., M. G. Trauzzi, A. E. Shrimpton, et al. 2006. Complete maternal uniparental isodisomy of chromosome 4 in a subject with major depressive disorder detected by high density SNP genotyping arrays. Am. J. Med. Genet. B: Neuropsychiatr. Genet. 141: 28-32.

Pato, C. N., F. A. Middleton, K. L. Gentile, et al. 2005. Genetic linkage of bipolar disorder to chromosome 6q22 is a consistent finding in Portuguese subpopulations and may generalize to broader populations. Am. J. Med. Genet. B Neuropsychiatr. Genet. 134: 119-121.

Petryshen, T. L., F. A. Middleton, A. R. Tahl, et al. 2005. Genetic investigation of chromosome 5q GABAA receptor subunit genes in schizophrenia. Mol. Psychiatry 10: 1074-1088.

Sklar, P., M. T. Pato, A. Kirby, et al. 2004. Genome-wide scan in Portuguese Island families identifies 5q31-5q35 as a susceptibility locus for schizophrenia and psychosis. Mol. Psychiatry 9: 213-218.

Genome-wide Disease Gene Mapping by Association Analysis

Hoh, J. & J. Ott. 2004. Genetic dissection of diseases: design and methods. Curr. Opin. Genet. Dev. 14: 229-232.

Klein, R. J., C. Zeiss, E. Y. Chew, et al. 2005. Complement factor H polymorphism in age-related macular degeneration. Science 308: 385-389.

Merikangas, K. R. & N. Risch, 2003. Genomic priorities and public health. Science 302: 599-601.

Ott, J. 2004. Issues in association analysis: error control in case-control association studies for disease gene discovery. Hum. Hered. 58: 171-174.

Tosic, M., J. Ott, S. Barral, et al. 2006. Schizophrenia and oxidative stress: Glutamate cysteine ligase modifier as a susceptibility gene. Am. J. Hum. Genet. 79: 586-592.

Willet, W.C. 2002. Balancing life-style and genomics research for disease prevention. Science 296: 695-698.

Yusuf, S., S. Hawken, S. Ounpuu, et al. 2004. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 364: 937-952.

Yusuf, S., S. Hawken, S. Ounpuu, et al. 2005. Obesity and the risk of myocardial infarction in 27,000 participants from 52 countries: a case-control study. Lancet 366: 1640-1649.

Zee, R. Y., J. Hoh, S. Cheng, et al. 2002. Multi-locus interactions predict risk for post-PTCA restenosis: an approach to the genetic analysis of common complex disease. Pharmacogenomics J. 2: 197-201.

Additional Background Reading

International HapMap Consortium. 2005. A haplotype map of the human genome. Nature 437: 1299-1320.

Mayeux, R. 2005. Mapping the new frontier: complex genetic disorders. J. Clin. Invest. 115: 1404-1457. Full Text

Risch, N. J. 2000. Searching for genetic determinants in the new millennium. Nature 405: 847-856.


Frank A. Middleton, PhD

State University of New York Upstate Medical University
email | web site | publications

Frank Middleton is an assistant professor in both the Department of Neuroscience & Physiology and the Department of Psychiatry & Behavioral Sciences at SUNY Upstate Medical University, where he also serves as director of the SUNY Microarray Core facility and the Center for Neuropsychiatric Genetics. Middleton has spent the past 16 years studying the anatomy, physiology, and molecular biology of brain circuits involved in neurologic and psychiatric disease. Over the past eight years, this research has focused heavily on the use of DNA microarrays for high-throughput genetic and functional genomic analyses.

Middleton received his PhD from Upstate Medical University in 1998. During his postdoctoral fellowship at the University of Pittsburgh, he was part of a team that published the first microarray study of schizophrenia (the second microarray study ever published on brain tissue). Middleton was lured back to SUNY Upstate as a faculty member with opportunities to establish a state of the art microarray core lab and join Carlos and Michele Pato in their pioneering work using population isolates to study genetic diseases.

Jürg Ott, PhD

The Rockefeller University
email | web site | publications

Jürg Ott is professor and head of the Laboratory of Statistical Genetics at The Rockefeller University. He is well known for his statistical/mathematical modeling work in gene mapping and is the author of the first generally available linkage analysis program (LIPED). He is an elected fellow of the American Association for the Advancement of Science, a member of HUGO, and currently serves on the Genome Study Section at NIH.

A native of Switzerland, Ott completed his PhD in zoology at the University of Zurich and a subsequent degree in biomathematics at the University of Washington. He has held positions at the University of Washington, the University of Basel, Columbia University, and the New York State Psychiatric Institute. He is the author of the text book Analysis of Human Genetic Linkage and coauthor (with Joseph Terwilliger) of Handbook of Human Genetic Linkage.

Catherine Zandonella

Catherine Zandonella is a science writer based in New York City, covering such topics as environmental science, public health, and applied technology. She has a master's degree in public health from the University of California, Berkeley. Zandonella has written for a number of publications, including New Scientist, The Scientist, and Nature.