title: Comparative full-length genome sequence analysis of 14 SARS coronavirus isolates and common mutations associated with putative origins of infection.
abstract: BACKGROUND
  The cause of severe acute respiratory syndrome (SARS) has been identified as a new coronavirus. Whole genome sequence analysis of various isolates might provide an indication of potential strain differences of this new virus. Moreover, mutation analysis will help to develop effective vaccines.
  
  
  METHODS
  We sequenced the entire SARS viral genome of cultured isolates from the index case (SIN2500) presenting in Singapore, from three primary contacts (SIN2774, SIN2748, and SIN2677), and one secondary contact (SIN2679). These sequences were compared with the isolates from Canada (TOR2), Hong Kong (CUHK-W1 and HKU39849), Hanoi (URBANI), Guangzhou (GZ01), and Beijing (BJ01, BJ02, BJ03, BJ04).
  
  
  RESULTS
  We identified 129 sequence variations among the 14 isolates, with 16 recurrent variant sequences. Common variant sequences at four loci define two distinct genotypes of the SARS virus. One genotype was linked with infections originating in Hotel M in Hong Kong, the second contained isolates from Hong Kong, Guangzhou, and Beijing with no association with Hotel M (p<0.0001). Moreover, other common sequence variants further distinguished the geographical origins of the isolates, especially between Singapore and Beijing.
  
  
  CONCLUSIONS
  Despite the recent onset of the SARS epidemic, genetic signatures are emerging that partition the worldwide SARS viral isolates into groups on the basis of contact source history and geography. These signatures can be used to trace sources of infection. In addition, a common variant associated with a non-conservative aminoacid change in the S1 region of the spike protein, suggests that immunological pressures might be starting to influence the evolution of the SARS virus in human populations.
authors.affiliation: Genome Institute of Singapore, Singapore.
authors.forename: Yi Jun
authors.initials: YJ
authors.lastname: Ruan
authors.forename: Chia Lin
authors.initials: CL
authors.lastname: Wei
authors.forename: Ai Ling
authors.initials: AL
authors.lastname: Ee
authors.forename: Vinsensius B
authors.initials: VB
authors.lastname: Vega
authors.forename: Herve
authors.initials: H
authors.lastname: Thoreau
authors.forename: Se Thoe Yun
authors.initials: ST
authors.lastname: Su
authors.forename: Jer-Ming
authors.initials: JM
authors.lastname: Chia
authors.forename: Patrick
authors.initials: P
authors.lastname: Ng
authors.forename: Kuo Ping
authors.initials: KP
authors.lastname: Chiu
authors.forename: Landri
authors.initials: L
authors.lastname: Lim
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.forename: Chan Kwai
authors.initials: CK
authors.lastname: Peng
authors.forename: Ean Oon Lynette
authors.initials: EO
authors.lastname: Lin
authors.forename: Ng Mah
authors.initials: NM
authors.lastname: Lee
authors.forename: Sin Leo
authors.initials: SL
authors.lastname: Yee
authors.forename: Lisa F P
authors.initials: LF
authors.lastname: Ng
authors.forename: Ren Ee
authors.initials: RE
authors.lastname: Chee
authors.forename: Lawrence W
authors.initials: LW
authors.lastname: Stanton
authors.forename: Philip M
authors.initials: PM
authors.lastname: Long
authors.forename: Edison T
authors.initials: ET
authors.lastname: Liu
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D016679:Genome, Viral; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D016366:Open Reading Frames; D010802:Phylogeny; D011110:Polymorphism, Genetic; D045473:Severe acute respiratory syndrome-related coronavirus / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D012846:Singapore