Sequencing Genome of Entire Family Reveals Parents Give Kids Fewer Gene Mutations Than Was Thought
ScienceDaily (Mar. 11, 2010) — Researchers at the University of Utah and other institutions have sequenced for the first time the entire genome of a family, enabling them to accurately estimate the average rate at which parents pass genetic mutations to their offspring and also identify precise locations where parental chromosomes exchange information that creates new combinations of genetic traits in their children.
Scientists have sequenced the entire genome of a family of four -- the parents, daughter, and son. (Credit: iStockphoto)
Led by scientists at the Seattle-based Institute for Systems Biology, the study, published March 11, 2010 in Science Express, sequenced the entire genome of a family of four -- the parents, daughter, and son. By comparing the parents' DNA sequences to those of their children, the researchers estimated with a high degree of certainty that each parent passes 30 mutations -- for a total of 60 -- to their offspring.
Scientists long had estimated that each parent passes 75 gene mutations to their children.
"That's the kind of power you get from looking at the whole genome," said Lynn B. Jorde, Ph.D., professor and chair of the Department of Human Genetics at the University of Utah School of Medicine. "The mutation rate was less than half of what we'd thought."
Genetic Clock
Most mutations, as far as medical researchers know, have no consequence for a child's health. But knowing the rate at which parents send on mutations to their offspring is critical information, according to Jorde. "The mutation rate is our clock, and every time it ticks we have a new genetic variant," he said. "We need to know how fast the clock ticks."
Everybody has about 22,000 genes, which contain the genetic blueprint for human life. This blueprint, called DNA, comprises more than 3 billion "base pairs" that determine genetic makeup. In1990, scientists worldwide began assembling the entire sequence of base pairs in all 22,000 human genes, a process called sequencing. When they completed the project in 2003, the scientists had put together the complete picture of the proper sequence of base pairs in the human genome.
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Published Online March 10, 2010
Science DOI: 10.1126/science.1186802
Analysis of Genetic Inheritance in a Family Quartet by Whole-Genome SequencingJared C. Roach,1,* Gustavo Glusman,1,* Arian F. A. Smit,1,* Chad D. Huff,1,2,* Robert Hubley,1Paul T. Shannon,1 Lee Rowen,1 Krishna P. Pant,3 Nathan Goodman,1 Michael Bamshad,4 Jay Shendure,5Radoje Drmanac,3 Lynn B. Jorde,2 Leroy Hood,1, David J. Galas1,
We analyzed the whole genome sequences of a family of four, consisting of two siblings and their parents. Family-based sequencing allowed us to delineate recombination sites precisely, identify 70% of the sequencing errors (resulting in 99.999% accuracy), and identify very rare single nucleotide polymorphisms. We also directly estimated a human intergeneration mutation rate of ~1.1 x 10-8 per position per haploid genome. Both offspring in this family have two recessive disorders—Miller syndrome, for which the gene was concurrently identified, and primary ciliary dyskinesia, for which causative genes have been previously identified. Family-based genome analysis enabled us to narrow the candidate genes for both of these Mendelian disorders to only four. Our results demonstrate the unique value of complete genome sequencing in families.
1 Institute for Systems Biology, Seattle, WA 98103, USA.
2 Department of Human Genetics, Eccles Institute of Human Genetics, University of Utah, Salt Lake City, UT 84109, USA.
3 Complete Genomics, Inc., Mountain View, CA 94043, USA.
4 Department of Pediatrics, University of Washington, Seattle, WA 98195, USA.
5 Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
* These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail: dgalas@systemsbiology.org (D.J.G.); lhood@systemsbiology.org (L.H.)
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