- Email: [email protected]
Of messages and meaning
COMMENT
round of duplication in Fig. 1 coneto this event. Such genome-
cla~sial pathway of complement activation that is normally activated lq lg. Ci is the component of the Iytic pathway. Therefore. the duplications
spends
wide duplication might have provided unique opportunities to create many accessory and rffector molecules of
in Fig. 1 created not only the MHC region of jawd vertebrates, but albo
the adaptive immune system. In hi5 classic monograph. Ohnot
at least nvo of the effector moleculrs of the humoral arm of the adaptive immune system. Chromobomal duplicutinn 1s an rtficient nay of making multiple molecules at once and. thus. is well suited for crating molecules
pointed out the impwzance of duplication in creating increasingly complex systems. The immune system i:, probably no exception to thi4 rule.
that function cooperatively. The immune syhtem of i~ved vcrtehr~tes
Acknowledgement Wethank Martin F.
appear5 to have exploited this property of ~hromobon13! duplication.
cuGm
Fktjnik tar dihand reading the mambcnpt.
Duplicationas an impetusto the emeqence of the adaptive immunesystem The immune \ystrm of i:t~le?lb fibhes seems to differ drarically from that of ja\vedvenehmrrs Nor only is the former expected to lack the tull> fledged MHC reglcd. hut appears to lack TCR. Ig and the lyw a> v.dl as the cl.,.. ,d pathnayz of complemcnt acti\auorPt’. Holiand et rrl Ii tlWW \Xih ~fOlWl>l~2 pr0pOXd ki genome-n ic!c duplication event dare to the ori::in of the ia\\rd vertd~rdc!.. It 6. therefore, poGbk that the hnt
MEETING
REPORT
Ofmessagesandmeaning GIH LM”WA,‘tOW
WORKSHOPONTHE IDLW~F~CAI’IO&’ OFTttAWtttBED SEQL!EWES.l:l~l\lll WI. I ii. 3-i cl-IOlitlc 19%
Presentations at this year‘.s tr;lnM nhed sequences workshop illustrated the maturdion ot the field The nvmy wccesws of large-scale transcriptmnal mapping effortb are now driving significant new effons in expression analysis d no\ and genes onto the physical map, and grnomic sequencing of
(Hospital
found only 10 genes in 3 region -10 “me\ larger. 3 3 hIi> deletion m lp36 .zu5pected of containing 3 tumor suppressor gene. E\en with tranhcript fragments in hand. however. deducing their relevance and relating them to genomic 5th cture might he difficult. This \VJS emphasized by Sherman Weissman (Yale Univ., USA) \\ho de~nhed a 700 I>p tmrwript, the f3144gene. that shows at least 30 nlternntively spliced form\ A second theme of the meeting concerned methods for largeXJk analysis of gene expression. Such methods are needed to define developmental timing and tissue specificity of expreh5ion. as well ad to document changes in expression due
MEETING to external stimuli or gene mutation.
REPORT
of re+wy %q”e”ces. Laurent Duret (Geneva Univ. Hospital, Switzerland) ib defining long (400 bp), highly conserved sequences found within 3’ UTIb of mRNAs. These might
Discussions at the meeting made clear several areas that require .swious attention if progress in tranbcriptiondl mapping is to Ix lx’u explaited. The EST database, dhEST.
FrJnce) has .screened.wver~l thowind arrayed cDNA clones with labelled RNA dxained from immune syswm tbhues of normal mice and mice lacking the TCR-CD3 zeta chain gene. Quanti-
have roles in transcriptional or tmnslationa~ regdation or m mRNA lo-
needs to contain a more complete representation of all genes. and in
calization. Wai-Choi Ixung (Tulane Univ., USA) discussed determining ener&y map” in mRNA and their use
patticulJr must contain the Ixmefide 5’ ends of mRNAs. Urnto Soares (Columbia Univ., USA) is exploring the
tative measurement of hybridization diffxences between the two types of mice has defined known and novel
in defining the sizes and kxations of oFen :md ckbrd configurations within mR..As. Such regions might
use of subtraction methods and size selection for the next generation of dhEST cDNA hlxaries and 13emhard
cI>NAs with significant differences in expre.ssion levels. Kevin Becker et N/. (NCHGR. USA) have used microarrays (miniaturized arrays of cDNAs on gla?* slides) simultaneously hybrid-
have functional or regulatory role*. and might also influence the efficiency of mKNA m reverse transcription reactions, and the repros-ntation ot the mRNA or rrgionh of the
Kern (German Cancer Research Center, Cennany) already has a subtantial fetal brain library constructed to contain 5’ end\ of mRNAs. .4 largexxle effort to apply northern analy-
ized with probes derived from two different RYA source.z labelled with
mRNA in cDNA libraries or RT-I’CR products. Encouraging progress in
hih and staged mouse embryo RNA tissue ilr s&r hybridization to a non-
different tluoresccnt tags. They have
promotei identification was diwuhhed
redundant set of &EST
dewrihed results comparing a mela-
hy Jim Fickett (SmithKline Beecham PhJrmaceuticals. USA) for myotubespecific regulatory regions. and by Thomas Werner flnst. fiir Sauergertirrgenetik. Gemxmy) for viral regulatory regions
also encouraged. Although no such program is currently in place, this would make a baseline time and place-of-expression profile available to all invesligators. There is also a compelling need for sophisticated
Guiseppc Bonani (Telethon Inst. Genetics and Metlicinc. Italy)
and flexible annotation of the Renomit sequence data now flooding
The use of complex ‘total mRNA probes to examine multiple cDNAs is one approach to this problem. Catherine Nguyen (CIML Luminy,
noma cell line xvith it\ tumor suppressed chromohom~-6-cc,nraining .subline, and are now Iookmg at developmenral expression of a zet of Ii0 zinc finger genes. Increasing use of army screwing \vill require development of high quality represen-
of
rative collections of cDNAs tram a broad range of sources. A second approach to esprehaion analysis ih differential d&play. Greg Sutcliffe (Scripps. USA) described one variation. the TOGA method (Total Gene Expre.zsion Analyhi~). a large-sc& technology that ih no\\ fluorescence-bJ.sed. automated and capdhle of identifying mKNA\ down to an abundance of less than 0.001%1. In a rchted discussion. Michael McClelland (Sidney Kimmcl Cancer Center. I’SA) presented data on xwiw:, paramcten. in particular the ‘Cot etfect’. whicl- must he cwefttlly controlled to reduce artifacts in quantatative I’CR and differential dihpkty technologies, Vital for the interpretation of gwwmic sequence and trxbcnptional maps ih sequence ha& tdentificatlon
described a strategy that exploas a model orgamhm databe. The DRES system (D~~~p!~i/~w&ed expreswd sequences) ider1tifie.s anti maps human EST5 that &play significant homokw to Dro.w&b eeneh associated xvith \vell-characterized IilUtJtiowJl phenotype% The corre.sponding human ESTs thub hecome candidates for human diseases locallzing to the xune realon For esample. thi5 analyhl:. hhwvh that the human FST homologous to the Dnw/~/dfi retinal degenerdon 15 gcnc maps to d region of diromo6om~ 11 \vhere three type> of retinopathie.s arc located. The full po\ber of this type of analysis xvill he rculizetl when Cmwwl7alxlitrs c4qprr.sand yeast mutational and espreshion datJ accumulate wil can he :~cceswd \xith wnilar edhe
<,,
.
.,
entries was
the databases. LastI;, the developmen, of rapid, informative and economical approaches to functional analysis of IarRe numbers of nove-el gene5 t.z now cntical if the ‘meaning of the mehhdw’ i:, to Ix detennined.
KathelfxnGardher [email protected]
Anthony Brookes ton~.brookes~,medgen.ttu.se
-Meeting reports in Trends in Genetics Meeting repom prwide highlightz of meetings of mtrrest to genrncists and dcvrlopmental biologists. We generally cwrr smaller meetings. although the topics .should Ix of widrbprrad Interest llx reports ax around 500 wvo&, and should bcus on the wprix~. the excitement:md the contmvr~~e.zIt the meet8ngwher than attempt to summarize the whole meeting. If you know alwut 3 meeting that we should cover. or if you would hke to xvriw 3 wpon for us. then plmse get tn towh Mark Patterson 7i-end~m Gmefrcs. Elwvicr TrencL\Jouma1.s.(fi Hills Road. Cambridge. LIK CR2 ILA. Tel: 44 1223 315961 ?? Fax: 44 1223 464130 ?? Email. TIGOelswier.co.uk
TIC
M,wc~
1997 Vot.. I3 No. 3
93
round of duplication in Fig. 1 coneto this event. Such genome-
cla~sial pathway of complement activation that is normally activated lq lg. Ci is the component of the Iytic pathway. Therefore. the duplications
spends
wide duplication might have provided unique opportunities to create many accessory and rffector molecules of
in Fig. 1 created not only the MHC region of jawd vertebrates, but albo
the adaptive immune system. In hi5 classic monograph. Ohnot
at least nvo of the effector moleculrs of the humoral arm of the adaptive immune system. Chromobomal duplicutinn 1s an rtficient nay of making multiple molecules at once and. thus. is well suited for crating molecules
pointed out the impwzance of duplication in creating increasingly complex systems. The immune system i:, probably no exception to thi4 rule.
that function cooperatively. The immune syhtem of i~ved vcrtehr~tes
Acknowledgement Wethank Martin F.
appear5 to have exploited this property of ~hromobon13! duplication.
cuGm
Fktjnik tar dihand reading the mambcnpt.
Duplicationas an impetusto the emeqence of the adaptive immunesystem The immune \ystrm of i:t~le?lb fibhes seems to differ drarically from that of ja\vedvenehmrrs Nor only is the former expected to lack the tull> fledged MHC reglcd. hut appears to lack TCR. Ig and the lyw a> v.dl as the cl.,.. ,d pathnayz of complemcnt acti\auorPt’. Holiand et rrl Ii tlWW \Xih ~fOlWl>l~2 pr0pOXd ki genome-n ic!c duplication event dare to the ori::in of the ia\\rd vertd~rdc!.. It 6. therefore, poGbk that the hnt
MEETING
REPORT
Ofmessagesandmeaning GIH LM”WA,‘tOW
WORKSHOPONTHE IDLW~F~CAI’IO&’ OFTttAWtttBED SEQL!EWES.l:l~l\lll WI. I ii. 3-i cl-IOlitlc 19%
Presentations at this year‘.s tr;lnM nhed sequences workshop illustrated the maturdion ot the field The nvmy wccesws of large-scale transcriptmnal mapping effortb are now driving significant new effons in expression analysis d no\ and genes onto the physical map, and grnomic sequencing of
(Hospital
found only 10 genes in 3 region -10 “me\ larger. 3 3 hIi> deletion m lp36 .zu5pected of containing 3 tumor suppressor gene. E\en with tranhcript fragments in hand. however. deducing their relevance and relating them to genomic 5th cture might he difficult. This \VJS emphasized by Sherman Weissman (Yale Univ., USA) \\ho de~nhed a 700 I>p tmrwript, the f3144gene. that shows at least 30 nlternntively spliced form\ A second theme of the meeting concerned methods for largeXJk analysis of gene expression. Such methods are needed to define developmental timing and tissue specificity of expreh5ion. as well ad to document changes in expression due
MEETING to external stimuli or gene mutation.
REPORT
of re+wy %q”e”ces. Laurent Duret (Geneva Univ. Hospital, Switzerland) ib defining long (400 bp), highly conserved sequences found within 3’ UTIb of mRNAs. These might
Discussions at the meeting made clear several areas that require .swious attention if progress in tranbcriptiondl mapping is to Ix lx’u explaited. The EST database, dhEST.
FrJnce) has .screened.wver~l thowind arrayed cDNA clones with labelled RNA dxained from immune syswm tbhues of normal mice and mice lacking the TCR-CD3 zeta chain gene. Quanti-
have roles in transcriptional or tmnslationa~ regdation or m mRNA lo-
needs to contain a more complete representation of all genes. and in
calization. Wai-Choi Ixung (Tulane Univ., USA) discussed determining ener&y map” in mRNA and their use
patticulJr must contain the Ixmefide 5’ ends of mRNAs. Urnto Soares (Columbia Univ., USA) is exploring the
tative measurement of hybridization diffxences between the two types of mice has defined known and novel
in defining the sizes and kxations of oFen :md ckbrd configurations within mR..As. Such regions might
use of subtraction methods and size selection for the next generation of dhEST cDNA hlxaries and 13emhard
cI>NAs with significant differences in expre.ssion levels. Kevin Becker et N/. (NCHGR. USA) have used microarrays (miniaturized arrays of cDNAs on gla?* slides) simultaneously hybrid-
have functional or regulatory role*. and might also influence the efficiency of mKNA m reverse transcription reactions, and the repros-ntation ot the mRNA or rrgionh of the
Kern (German Cancer Research Center, Cennany) already has a subtantial fetal brain library constructed to contain 5’ end\ of mRNAs. .4 largexxle effort to apply northern analy-
ized with probes derived from two different RYA source.z labelled with
mRNA in cDNA libraries or RT-I’CR products. Encouraging progress in
hih and staged mouse embryo RNA tissue ilr s&r hybridization to a non-
different tluoresccnt tags. They have
promotei identification was diwuhhed
redundant set of &EST
dewrihed results comparing a mela-
hy Jim Fickett (SmithKline Beecham PhJrmaceuticals. USA) for myotubespecific regulatory regions. and by Thomas Werner flnst. fiir Sauergertirrgenetik. Gemxmy) for viral regulatory regions
also encouraged. Although no such program is currently in place, this would make a baseline time and place-of-expression profile available to all invesligators. There is also a compelling need for sophisticated
Guiseppc Bonani (Telethon Inst. Genetics and Metlicinc. Italy)
and flexible annotation of the Renomit sequence data now flooding
The use of complex ‘total mRNA probes to examine multiple cDNAs is one approach to this problem. Catherine Nguyen (CIML Luminy,
noma cell line xvith it\ tumor suppressed chromohom~-6-cc,nraining .subline, and are now Iookmg at developmenral expression of a zet of Ii0 zinc finger genes. Increasing use of army screwing \vill require development of high quality represen-
of
rative collections of cDNAs tram a broad range of sources. A second approach to esprehaion analysis ih differential d&play. Greg Sutcliffe (Scripps. USA) described one variation. the TOGA method (Total Gene Expre.zsion Analyhi~). a large-sc& technology that ih no\\ fluorescence-bJ.sed. automated and capdhle of identifying mKNA\ down to an abundance of less than 0.001%1. In a rchted discussion. Michael McClelland (Sidney Kimmcl Cancer Center. I’SA) presented data on xwiw:, paramcten. in particular the ‘Cot etfect’. whicl- must he cwefttlly controlled to reduce artifacts in quantatative I’CR and differential dihpkty technologies, Vital for the interpretation of gwwmic sequence and trxbcnptional maps ih sequence ha& tdentificatlon
described a strategy that exploas a model orgamhm databe. The DRES system (D~~~p!~i/~w&ed expreswd sequences) ider1tifie.s anti maps human EST5 that &play significant homokw to Dro.w&b eeneh associated xvith \vell-characterized IilUtJtiowJl phenotype% The corre.sponding human ESTs thub hecome candidates for human diseases locallzing to the xune realon For esample. thi5 analyhl:. hhwvh that the human FST homologous to the Dnw/~/dfi retinal degenerdon 15 gcnc maps to d region of diromo6om~ 11 \vhere three type> of retinopathie.s arc located. The full po\ber of this type of analysis xvill he rculizetl when Cmwwl7alxlitrs c4qprr.sand yeast mutational and espreshion datJ accumulate wil can he :~cceswd \xith wnilar edhe
<,,
.
.,
entries was
the databases. LastI;, the developmen, of rapid, informative and economical approaches to functional analysis of IarRe numbers of nove-el gene5 t.z now cntical if the ‘meaning of the mehhdw’ i:, to Ix detennined.
KathelfxnGardher [email protected]
Anthony Brookes ton~.brookes~,medgen.ttu.se
-Meeting reports in Trends in Genetics Meeting repom prwide highlightz of meetings of mtrrest to genrncists and dcvrlopmental biologists. We generally cwrr smaller meetings. although the topics .should Ix of widrbprrad Interest llx reports ax around 500 wvo&, and should bcus on the wprix~. the excitement:md the contmvr~~e.zIt the meet8ngwher than attempt to summarize the whole meeting. If you know alwut 3 meeting that we should cover. or if you would hke to xvriw 3 wpon for us. then plmse get tn towh Mark Patterson 7i-end~m Gmefrcs. Elwvicr TrencL\Jouma1.s.(fi Hills Road. Cambridge. LIK CR2 ILA. Tel: 44 1223 315961 ?? Fax: 44 1223 464130 ?? Email. TIGOelswier.co.uk
TIC
M,wc~
1997 Vot.. I3 No. 3
93