RESEARCH HIGHLIGHTS HIGHLIGHT ADVISORS SEAN B. CARROLL UNIVERSITY OF WISCONSIN, USA NANCY J. COX UNIVERSITY OF CHICAGO, USA RALPH J. GREENSPAN THE NEUROSCIENCES INSTITUTE, CALIFORNIA, USA YOSHIHIDE HAYASHIZAKI RIKEN GENOMIC SCIENCES CENTER, JAPAN PETER KOOPMAN UNIVERSITY OF QUEENSLAND, AUSTRALIA LEONID KRUGLYAK FRED HUTCHINSON CANCER RESEARCH CENTER, USA BARBARA MEYER UNIVERSITY OF CALIFORNIA, BERKELEY, USA JOHN QUAKENBUSH THE INSTITUTE FOR GENOMIC RESEARCH, USA NADIA ROSENTHAL EMBL MONTEROTONDO, ITALY MARC VIDAL DANA-FARBER CANCER INSTITUTE, BOSTON, USA VIRGINIA WALBOT STANFORD UNIVERSITY, USA DETLEF WEIGEL MAX PLANCK INSTITUTE FOR DEVELOPMENTAL BIOLOGY, GERMANY PHIL ZAMORE UNIVERSITY OF MASSACHUSETTS, USA LEONARD I. ZON CHILDREN’S HOSPITAL, BOSTON, USA 250 | APRIL 2005 | VOLUME 6 www.nature.com/reviews/genetics The DNA sequence of the human X chromosome — the fourteenth human chromosome to have its genetic line-up deciphered — has now been published. The sequence reveals the many unique features of this chromosome and could provide use- ful insights into X-chromosome inactivation and the origin and evolution of mammalian sex chromosomes. The sequencing effort, which was carried out using shotgun and both BAC- and PAC-based sequencing, shows that this ~155-Mb chromosome is surprisingly gene poor. With only 1,098 annotated genes its gene density is among the lowest of all the human chromosomes that have been annotated. Consistent with its low gene density, the frequency of pre- dicted CpG islands is exactly half the estimated genome average. The X chromosome is also highly enriched in interspersed repeats, particularly those of the LINE1 class. The distrib- ution of these repeats on the chromosome is consistent with a proposed role in X-chromosome inactivation. The origin of the mammalian X chromosome is fascinating for sev- eral reasons, including its unique dosage-compensation mechanism and its relationship to the human Y chromosome. The authors con- firm that, indeed, the X chromosome has by far the most conserved gene arrangement in placental mam- mals. Sequence alignments between the human X chromosome and the chicken genome corroborates the autosomal origin of the mammalian sex chromosomes before they were recruited into a chromosomal system for sex determination. Further analy- sis provides valuable information on the timing and location of a series of rearrangements that have taken place on this chromosome over the last 300 million years, and on the pro- gressive loss of recombination between the sex chromosomes that allowed the X and Y chromosomes to evolve independently. The X chromosome holds a unique place in the history of medical genetics. X-linked diseases are rela- tively easy to recognize owing to their mode of inheritance, and the phe- notypic consequences of recessive, X-linked mutations are revealed in males. Therefore, despite its gene-poor An X ordinary sequence GENOMICS content, almost 10% of diseases with a Mendelian pattern of inheritance have been assigned to the X chromosome. The annotation of the X chromosome will accelerate the process of dis- covering new genes that are involved in rare genetic disorders. Moreover, the study of the sequence could help us to understand the mysteries that underlie X-chromosome inactivation, genomic imprinting and sex-chromosome evolution. Taking advantage of further genome sequences, compar- isons could be made to unravel the dif- ferent evolutionary forces that shape sex chromosomes in mammalian and non-mammalian systems. Ekat Kritikou References and links ORIGINAL RESEARCH PAPER Ross, M. T. et al. The DNA sequence of the human X chromosome. Nature 17 March 2005 (doi:10.1038/nature 03440) WEB SITES Human X Chromosome Project: http://www.sanger.ac.uk/HGP/ChrX VEGA database: http://vega.sanger.ac.uk/Homo_sapiens © 2005 Nature Publishing Group

Genomics: An X ordinary sequence

Download PDF Report

Upload
ekat
View
213
Download
0

Embed Size (px)

Citation preview

Page 1: Genomics: An X ordinary sequence

RESEARCH

HIGHLIGHTS

HIGHLIGHT ADVISORS

SEAN B. CARROLL

UNIVERSITY OF WISCONSIN,USA

NANCY J. COX

UNIVERSITY OF CHICAGO, USA

RALPH J. GREENSPAN

THE NEUROSCIENCESINSTITUTE, CALIFORNIA, USA

YOSHIHIDE HAYASHIZAKI

RIKEN GENOMIC SCIENCESCENTER, JAPAN

PETER KOOPMAN

UNIVERSITY OF QUEENSLAND,AUSTRALIA

LEONID KRUGLYAK

FRED HUTCHINSON CANCERRESEARCH CENTER, USA

BARBARA MEYER

UNIVERSITY OF CALIFORNIA,BERKELEY, USA

JOHN QUAKENBUSH

THE INSTITUTE FOR GENOMICRESEARCH, USA

NADIA ROSENTHAL

EMBL MONTEROTONDO, ITALY

MARC VIDAL

DANA-FARBER CANCERINSTITUTE, BOSTON, USA

VIRGINIA WALBOT

STANFORD UNIVERSITY, USA

DETLEF WEIGEL

MAX PLANCK INSTITUTE FORDEVELOPMENTAL BIOLOGY,GERMANY

PHIL ZAMORE

UNIVERSITY OFMASSACHUSETTS, USA

LEONARD I. ZON

CHILDREN’S HOSPITAL,BOSTON, USA

250 | APRIL 2005 | VOLUME 6 www.nature.com/reviews/genetics

The DNA sequence of the human X chromosome — the fourteenthhuman chromosome to have itsgenetic line-up deciphered — has nowbeen published. The sequence revealsthe many unique features of thischromosome and could provide use-ful insights into X-chromosome inac-tivation and the origin and evolutionof mammalian sex chromosomes.

The sequencing effort, which wascarried out using shotgun and bothBAC- and PAC-based sequencing,shows that this ~155-Mb chromo-some is surprisingly gene poor. Withonly 1,098 annotated genes its genedensity is among the lowest of all thehuman chromosomes that have beenannotated. Consistent with its lowgene density, the frequency of pre-dicted CpG islands is exactly halfthe estimated genome average. The X chromosome is also highly enrichedin interspersed repeats, particularlythose of the LINE1 class. The distrib-ution of these repeats on the chromo-some is consistent with a proposedrole in X-chromosome inactivation.

The origin of the mammalian X chromosome is fascinating for sev-eral reasons, including its uniquedosage-compensation mechanismand its relationship to the human Y chromosome. The authors con-firm that, indeed, the X chromo-some has by far the most conservedgene arrangement in placental mam-mals. Sequence alignments betweenthe human X chromosome and thechicken genome corroborates theautosomal origin of the mammalian

sex chromosomes before they wererecruited into a chromosomal systemfor sex determination. Further analy-sis provides valuable information onthe timing and location of a series ofrearrangements that have takenplace on this chromosome over thelast 300 million years, and on the pro-gressive loss of recombination betweenthe sex chromosomes that allowedthe X and Y chromosomes to evolveindependently.

The X chromosome holds aunique place in the history of medicalgenetics. X-linked diseases are rela-tively easy to recognize owing to theirmode of inheritance, and the phe-notypic consequences of recessive,X-linked mutations are revealed inmales. Therefore, despite its gene-poor

An X ordinary sequence

G E N O M I C S content, almost 10% of diseaseswith a Mendelian pattern of inheri-tance have been assigned to the X chromosome.

The annotation of the X chromo-some will accelerate the process of dis-covering new genes that are involvedin rare genetic disorders. Moreover,the study of the sequence could helpus to understand the mysteries thatunderlie X-chromosome inactivation,genomic imprinting and sex-chromo-some evolution. Taking advantage offurther genome sequences, compar-isons could be made to unravel the dif-ferent evolutionary forces that shapesex chromosomes in mammalian andnon-mammalian systems.

Ekat Kritikou

References and linksORIGINAL RESEARCH PAPER Ross, M. T. et al.The DNA sequence of the human X chromosome.Nature 17 March 2005 (doi:10.1038/nature 03440)WEB SITESHuman X Chromosome Project:http://www.sanger.ac.uk/HGP/ChrXVEGA database:http://vega.sanger.ac.uk/Homo_sapiens