DNA sequence and analysis of human chromosome 8.
The International Human Genome Sequencing Consortium (IHGSC) recently completed a sequence of the human genome. As part of this project, we have focused on chromosome 8. Although some chromosomes exhibit extreme characteristics in terms of length, gene content, repeat content and fraction segmentally duplicated, chromosome 8 is distinctly typical in character, being very close to the genome median in each of these aspects. This work describes a finished sequence and gene catalogue for the chromosome, which represents just over 5% of the euchromatic human genome. A unique feature of the chromosome is a vast region of approximately 15 megabases on distal 8p that appears to have a strikingly high mutation rate, which has accelerated in the hominids relative to other sequenced mammals. This fast-evolving region contains a number of genes related to innate immunity and the nervous system, including loci that appear to be under positive selection--these include the major defensin (DEF) gene cluster and MCPH1, a gene that may have contributed to the evolution of expanded brain size in the great apes. The data from chromosome 8 should allow a better understanding of both normal and disease biology and genome evolution.
Nusbaum
Chad
C
Broad Institute of MIT and Harvard, 320 Charles St, Cambridge, Massachusetts 02141, USA. chad@broad.mit.edu
Mikkelsen
Tarjei S
TS
Zody
Michael C
MC
Asakawa
Shuichi
S
Taudien
Stefan
S
Garber
Manuel
M
Kodira
Chinnappa D
CD
Schueler
Mary G
MG
Shimizu
Atsushi
A
Whittaker
Charles A
CA
Chang
Jean L
JL
Cuomo
Christina A
CA
Dewar
Ken
K
FitzGerald
Michael G
MG
Yang
Xiaoping
X
Allen
Nicole R
NR
Anderson
Scott
S
Asakawa
Teruyo
T
Blechschmidt
Karin
K
Bloom
Toby
T
Borowsky
Mark L
ML
Butler
Jonathan
J
Cook
April
A
Corum
Benjamin
B
DeArellano
Kurt
K
DeCaprio
David
D
Dooley
Kathleen T
KT
Dorris
Lester
L
Engels
Reinhard
R
Glöckner
Gernot
G
Hafez
Nabil
N
Hagopian
Daniel S
DS
Hall
Jennifer L
JL
Ishikawa
Sabine K
SK
Jaffe
David B
DB
Kamat
Asha
A
Kudoh
Jun
J
Lehmann
Rüdiger
R
Lokitsang
Tashi
T
Macdonald
Pendexter
P
Major
John E
JE
Matthews
Charles D
CD
Mauceli
Evan
E
Menzel
Uwe
U
Mihalev
Atanas H
AH
Minoshima
Shinsei
S
Murayama
Yuji
Y
Naylor
Jerome W
JW
Nicol
Robert
R
Nguyen
Cindy
C
O'Leary
Sinéad B
SB
O'Neill
Keith
K
Parker
Stephen C J
SC
Polley
Andreas
A
Raymond
Christina K
CK
Reichwald
Kathrin
K
Rodriguez
Joseph
J
Sasaki
Takashi
T
Schilhabel
Markus
M
Siddiqui
Roman
R
Smith
Cherylyn L
CL
Sneddon
Tam P
TP
Talamas
Jessica A
JA
Tenzin
Pema
P
Topham
Kerri
K
Venkataraman
Vijay
V
Wen
Gaiping
G
Yamazaki
Satoru
S
Young
Sarah K
SK
Zeng
Qiandong
Q
Zimmer
Andrew R
AR
Rosenthal
Andre
A
Birren
Bruce W
BW
Platzer
Matthias
M
Shimizu
Nobuyoshi
N
Lander
Eric S
ES
D000818:Animals; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D020451:Contig Mapping; D004276:DNA, Satellite / Q000235:genetics; D023082:Defensins / Q000235:genetics; D022041:Euchromatin / Q000235:genetics; D019143:Evolution, Molecular; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics; D017422:Sequence Analysis, DNA
D004276:DNA, Satellite; D023082:Defensins; D022041:Euchromatin