along with the background and rationale for its fish model, the services provided are discussed, and information given on points of contact and web sites. THE  FUGU  GENOMICS  GROUP,  HGMP RESOURCE  CENTRE,  WELLCOME  GENOME CAMPUS,  HINXTON,  CAMBRIDGE, UK Program  Description Hinegardner (1968) assayed the haploid DNA content of a large number of teleosts and found that many species had small genomes, especially the tetraodontoid (four-toothed) fishes,  which  include  the  puffers.  In  Japan,  the  puffer  fish (Fugu  rubripes)  is  a  gastronomic  delicacy  that  contains  a potent  visceral  neurotoxin  that  kills  several  people  each year. Estimates of the DNA content of Fugu indicate that its genome  size  lies  between  4  and  500  Mb  (Hinegardner, 1968). However, this species should be viewed as a model genome,  not  as  a  model  organism,  as  experimentation  on Fugu is difficult. It grows to a kilogram within the first year, becomes  sexually  mature  in  three  years,  and  is  difficult  to maintain using traditional methods. The Fugu genome has about the same number of genes as  many  mammalian  genomes  but  the  genes  generally  are smaller (Clark and Elgar, 2000). Although coding sequences are  about  the  same  size,  intron  sizes  are  greatly  reduced, intergenic  distances  are  much  smaller,  and  there  is  little repetitive DNA, virtually none of which is dispersed (Bren- ner, 1993; Edwards et al., 1998; Elgar et al., 1995). Hence, cloning by PCR of all possible members of a particular gene family (Macrae and Brenner, 1995: Venkatesh et al., 1996; Cottage  et  al.,  1999)  is  much  easier  in  such  a  compact genome as that of Fugu. Due to the large evolutionary distance between mam- mals  and  Fugu  (approximately  400  Myr),  conserved  non- coding  elements  presumably  have  a  high  probability  of functional  significance,  and  so  provide  a  minimal  data  set with  which  to  study  promoter  and  regulatory  elements (Marshall et al., 1994; Aparicio et al., 1995; Venkatesh et al., 1997; Rowitch et al., 1998). The extent of synteny between Fugu  and  humans  is  questionable,  with  examples  of  com- plete  conservation  of  gene  content,  order,  and  orientation (Miles et al., 1998), altered gene order (Gellner and Bren- ner, 1999), and extensive rearrangements (Gilley and Fried, 1999). This variable syntechnic situation should not be dis- missed as too confusing to explain. Closer examination of particular regions of the genome, such as the MHC class I region, can provide clues to the pattern of evolution of the vertebrate genome (Clark et al., 2000). The complete geno- mic  sequence  of  both  Fugu  and  humans  will  provide  an- swers to the question of synteny and produce copious data for  evolutionary  geneticists.  Four-way  comparisons  of  ge- nomic sequences among humans and some fishes, includ- ing  zebrafish,  Fugu,  and  the  freshwater  puffer  fish  (Tetra- odon  nigroviridis),  will  give  us  a  generalized  picture  of  the size  of  homologous  gene  blocks  shared  by  mammals  and fish. Additionally, comparisons restricted to these three fish species also will indicate the extent of conservation of syn- teny within them, which will be of great interest for posi- tional  cloning  studies  in  other  fishes,  particularly  for  re- search on resistance and susceptibility to disease. The  Fugu  Genomics  Group,  HGMP  Resource  Centre, in Cambridge, seeks to demonstrate the advantages of using the Japanese puffer fish (Fugu rubripes) as a model for in- terpreting and analyzing vertebrate genomic data, with spe- cial  reference  to  the  Human  Genome  Project.  The  group also offers Fugu genomic resources free to the research com- munity. The group is part of a consortium led by the Joint Genome Institute (JGI) of the US Department of Energy to sequence  the  Fugu  genome.  JGI’s  aim  is  to  completely  se- quence the Fugu genome by using the shotgun sequencing approach  and  to  make  the  draft  sequence  data  publicly available  in  2001.  All  sequence  data  will  be  posted  on  the JGI  web  site  (http://www.jgi.doe.gov).  Having  data  on  the full genomic sequence will clearly alter the direction of the research  of  the  genomics  group;  the  initiation  of  an  EST program  will  facilitate  a  move  toward  functional  analyses. Currently, scientists in the group are particularly interested in three regions in the Fugu genome comparable to human chromosomes  11p,  20q,  and  6p21.3  (the  major  histocom- patibility complex). Their other interests include G-protein coupled  receptors,  conserved  noncoding  regulatory  ele- ments, and gene evolution and duplication in fish. Services The services and products offered from the Distributed Services  Group  at  the  HGMP  include  the  following:  (1)  a cosmid library of 75,000 clones with an average insert size of 40 kb, equivalent to 7× genome coverage, available as grid- ded  filter  sets;  (2)  high-molecular-weight  Fugu  genomic DNA  for  Southern  blots  or  PCR  in  50-µg  aliquots  in  TE buffer  and  agarose  plugs  for  constructing  PFGE/libraries; and (3) nonnormalized cDNA libraries, available as gridded S240 William E. Hawkins et al. Next >>