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Structural Variation

Program Rationale

The Human Genome Project provided information vital to a broad spectrum of research underlying human biology and medicine. As a next step, large-scale study of the variation of genetic information between individual humans will provide insight into the effect that natural variation in genome structure has on human health and susceptibility to disease.

Information about human variation has been used to construct a haplotype map of the human genome, HapMap, which will speed the ability to map genetic variantsassociated with disease, drug response, and other medically important phenotypes to an unprecedented degree.

However, we still do not completely understand the "normal" range of human variation present in populations to provide a basis for understanding the variations that result in disease.

The sequence-based Survey of Human Structural Variation aims to characterize common structural variants that are larger than 5 kb, such as multi-base insertions/deletions, inversions, translocations, and duplications. The approach entails sequencing the ends of fosmids and BACs from multiple individuals. This strategy can be efficiently scaled with current technology and is complementary to efforts to obtain human structural variation information by other technologies.

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Program Implementation and Management

The initial implementation plan for this initiative calls for sequencing ~0.4X coverage in fosmid ends from up to 21 individuals, and BAC ends for a few additional individuals. End sequence will be compared to the reference sequence. Clones that are discrepant with the reference will be fully sequenced. In addition ~5 Mb worth of regions will be selected and fully sequenced from 48 individuals, in order to provide a standard for studies of structural variation. Clones that identify structural variants will be retained and provided as a community resource. In the longer term, the structural variants will be genotyped for integration into the HapMap.

However, this large multi-year initiative must remain flexible enough to take into account new information and analyses. In addition, new sequencing technologies may offer significant advantages towards pursuing the overall aims., NHGRI has thus assembled a steering group to help implement and guide this initiative (See: Group Rosters). The steering group is charged with monitoring progress, analyzing the data to ensure that the goals are being met, suggesting mid-course modifications where they are scientifically justified, selecting the regions for full sequencing, and consulting with NHGRI about which clone resources should be maintained for distribution.

A white paper (See: Human Genome Structural Variation ) provides a full project description.

As with all NHGRI initiatives and projects, data are made available immediately through the NCBI Trace Archive. []

Samples are available through the Coriell Institute.

A full list of HapMap individuals who are the subject of this project is below.

Table: Fosmid libraries used for the structural variation survey.

Order Cell Culture ID DNA Sample ID Population Sex Family Status
1 GM18517 [] NA18517 Yoruba F Y013 Complete
2 GM18507 [] NA18507 Yoruba M Y009 Complete
3 GM18956 [] NA18956 Japanese F ------ Complete
4 GM19240 [] NA19240 Yoruba F Y117 Complete
5 GM12878 [] NA12878 CEPH F 1463 Complete
6 GM18555 [] NA18555 Han Chinese F ------ Complete
7 GM19129 [] NA19129 Yoruba F Y077 Complete
8 GM12156 [] NA12156 CEPH F 1408 Complete
9 GM18502 [] NA18502 Han Chinese F ------ Complete
10 GM10847 [] NA10847 CEPH F 1334 Ongoing
11 GM11840 [] NA11840 CEPH F 1349 Ongoing
12 GM11832 [] NA11832 CEPH F 1350 Ongoing
13 GM11832 [] NA11832 CEPH F 1362 Ongoing
14 GM18942 [] NA18942 Japanese F ----- Ongoing
15 GM18947 [] NA18947 Japanese F ----- Ongoing
16 GM18564 [] NA18564 Han Chinese F ----- Ongoing
17 GM18573 [] NA18573 Han Chinese F ----- Ongoing
18 GM18502 [] NA18502 Yoruba F Y004 Ongoing
19 GM18523 [] NA18523 Yoruba F Y016 Ongoing
20 GM18861 [] NA18861 Yoruba F Y024 Ongoing
21 GM19102 [] NA19102 Yoruba F Y042 Ongoing

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Program Contacts

Adam Felsenfeld, Ph.D.
Program Director

Lisa Brooks, Ph.D.
Program Director

Jane Peterson, Ph.D.

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Last Updated: January 21, 2014