Analysis of Genetic Inheritance in a Family Quartet by Whole-genome Sequencing

Overview

Journal Science

Specialty Science

Date 2010 Mar 12

PMID 20220176

Citations 552

Authors

Jared C Roach

Gustavo Glusman

Arian F A Smit

Chad D Huff

Robert Hubley

Paul T Shannon

Lee Rowen

Krishna P Pant

Nathan Goodman

Michael Bamshad

Jay Shendure

Radoje Drmanac

Lynn B Jorde

Leroy Hood

David J Galas

Affiliations

Soon will be listed here.

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.

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