Analysis of genetic inheritance in a family quartet by whole-genome sequencing
Science, 2010•science.org
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× 10− 8 per position per haploid genome. Both offspring
in this family have two recessive disorders: Miller syndrome, for which the gene was …
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× 10− 8 per position per haploid genome. Both offspring
in this family have two recessive disorders: Miller syndrome, for which the gene was …
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 × 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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