Format

Send to

Choose Destination
Science. 2010 Apr 30;328(5978):636-9. doi: 10.1126/science.1186802. Epub 2010 Mar 10.

Analysis of genetic inheritance in a family quartet by whole-genome sequencing.

Author information

1
Institute for Systems Biology, Seattle, WA 98103, USA.

Abstract

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 approximately 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 value of complete genome sequencing in families.

Comment in

PMID:
20220176
PMCID:
PMC3037280
DOI:
10.1126/science.1186802
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center