The characterization of twenty sequenced human genomes.
We present the analysis of twenty human genomes to evaluate the prospects for identifying rare functional variants that contribute to a phenotype of interest. We sequenced at high coverage ten "case" genomes from individuals with severe hemophilia A and ten "control" genomes. We summarize the number of genetic variants emerging from a study of this magnitude, and provide a proof of concept for the identification of rare and highly-penetrant functional variants by confirming that the cause of hemophilia A is easily recognizable in this data set. We also show that the number of novel single nucleotide variants (SNVs) discovered per genome seems to stabilize at about 144,000 new variants per genome, after the first 15 individuals have been sequenced. Finally, we find that, on average, each genome carries 165 homozygous protein-truncating or stop loss variants in genes representing a diverse set of pathways.
Pelak
Kimberly
K
Center for Human Genome Variation, Duke University School of Medicine, Durham, North Carolina, United States of America.
Shianna
Kevin V
KV
Ge
Dongliang
D
Maia
Jessica M
JM
Zhu
Mingfu
M
Smith
Jason P
JP
Cirulli
Elizabeth T
ET
Fellay
Jacques
J
Dickson
Samuel P
SP
Gumbs
Curtis E
CE
Heinzen
Erin L
EL
Need
Anna C
AC
Ruzzo
Elizabeth K
EK
Singh
Abanish
A
Campbell
C Ryan
CR
Hong
Linda K
LK
Lornsen
Katharina A
KA
McKenzie
Alexander M
AM
Sobreira
Nara L M
NL
Hoover-Fong
Julie E
JE
Milner
Joshua D
JD
Ottman
Ruth
R
Haynes
Barton F
BF
Goedert
James J
JJ
Goldstein
David B
DB
D001483:Base Sequence; D016022:Case-Control Studies; D056915:DNA Copy Number Variations / Q000235:genetics; D030541:Databases, Genetic; D005091:Exons / Q000235:genetics; D005169:Factor VIII / Q000235:genetics; D020440:Gene Duplication / Q000235:genetics; D055786:Gene Knockout Techniques; D005828:Genetics, Population; D015894:Genome, Human / Q000235:genetics*; D005838:Genotype; D006467:Hemophilia A / Q000235:genetics; D006801:Humans; D054643:INDEL Mutation / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D016366:Open Reading Frames / Q000235:genetics; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017422:Sequence Analysis, DNA
D005169:Factor VIII