The Genom of Homo sapiens.pdf

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DOWN SYNDROME AND HUMAN CHROMOSOME 21 427The extensive and systematic functional and evolutionarystudy of CNGs will enhance our understanding ofthese important genomic elements. Further studies willaddress the contribution of CNGs to health and disease,both Mendelian and complex phenotypes; in addition,they may reveal their potential involvement in the differentphenotypes of trisomy 21.Number of genesEXPRESSION ATLAS OF MOUSE ORTHOLOGSOF Hsa21 GENESThe completion of the human genome, and the continuedeffort to identify all the human genes, present now theformidable task of the elucidation of the function of allthese genes. The next logical level of gene annotation isto determine the expression pattern of each individualgene in terms of tissue, cellular, and temporal specificity.High-resolution methods, such as RNA in situ hybridization(ISH) provide an accurate description of the spatiotemporaldistribution of transcripts as well as a threedimensional“in vivo” gene expression overview.We set out to analyze systematically the expressionpattern of genes from the entire Hsa21. We chose to developthis gene expression atlas using the mouse orthologsof the Hsa21 genes; these genes map in the syntenicregion of the mouse genome; i.e., segments ofMmu16, Mmu17, and Mmu10. A total of 161 murinegenes out of the 178 confirmed human genes were studied.The expression atlas, which was a collaborative effortwith the laboratories of A. Ballabio, TIGEM, Naples,and G. Eichele, Max Planck Institute, Hannover, consistsof (1) whole-mount ISH of mouse embryos at E9.5 andE10.5; (2) ISH on serial sagittal sections of E14.5; and(3)RT-PCR in four developmental stages (E8.5, E9.5,E12.5, and E19) and 12 adult tissues (brain, heart, kidney,thymus, liver, stomach, muscle, lung, testis, ovary, skin,and eyes). All the data (gene list, original ISH images, annotationtables, details on probes and oligonucleotideprimers) are publicly available through Web siteshttp://www.tigem.it/ch21exp/ or http://www.nature.com/nature (Reymond et al. 2002).By whole-mount ISH at E10.5, patterned (regional)gene expression was observed in 28%, and ubiquitous expressionin 24%, of genes; furthermore, weak ubiquitousand strong regional expression was observed in 47% ofgenes. The ISH in tissue sections at E14.5 revealed patterned(regional) gene expression in 42%, ubiquitous expressionin 13%, and combined weak ubiquitous andstrong regional expression in 9% of genes. The highestnumbers of genes with a restricted expression patternwere observed in the brain, the eye, and the gut at allstages (Fig. 4a). The RT-PCR analysis resulted in an averageof eight adult tissues per gene (Fig. 4b). The transcriptomesof the brain and kidney showed the highestcomplexity, each tissue expressing 85% of the 161 genesexamined. Muscle, as expected, had the lowest transcriptomecomplexity, since only 21% of genes examinedwere expressed there.Figure 4. (a) Number of the Hsa21 mouse orthologous genesanalyzed by RT-PCR expressed in 0, 1, 2–3, 4–5, 6–7, 8–9, and10–12 adult tissues. (b) Percentage of the Hsa21 mouse orthologousgenes analyzed by RT-PCR identified in each murine adulttissue. (c) Schematic representation of a cluster of Hsa21 orthologousgenes (Pdxk to Hrmtl1) mapping to Mmu10 that show asignificant absence of expression in muscle (p = 0.02). Mb distanceswere published in Hattori et al. (2000). Genes are representedby gray arrows. (Adapted from Reymond et al. 2002.)Unexpectedly, we found genomic regions containingclusters of genes with similar expression patterns. Regionscontaining either co-silenced or co-expressed geneswere observed. For example, RT-PCR analysis identifieda 3.9-Mb (from genes B3galt5 to Hsf2bp) and a 4.3-Mbregion (from genes Pdxk to Hrmtl1, Fig. 4c) in which allgenes were not expressed in heart (p
428 ANTONARAKIS ET AL.Figure 5. Sample amplification plots from human pilot study. Each panel shows the results from three genes in two individuals, with12 replicates per gene. For each gene, the different shadings represent two individuals. Note, for example, the large expression differencein the two individuals for ABCG1 relative to CSTB and AGPAT1.
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ForewordIn 2001, as we considered t
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The Finished Genome Sequence of Hom
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4 ROGERSFigure 2. Accumulation of h
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6 ROGERSFigure 4. Sequencing center
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8 ROGERSabcFigure 5. Ensembl view o
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10 ROGERS2000. Analysis of vertebra
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The Human Genome: Genes, Pseudogene
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VARIATION ON CHROMOSOME 7 15rived f
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VARIATION ON CHROMOSOME 7 17DNAs an
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VARIATION ON CHROMOSOME 7 19expecte
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VARIATION ON CHROMOSOME 7 21Drosoph
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Mutational Profiling in the Human G
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HUMAN MUTATIONAL PROFILING 25Anothe
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HUMAN MUTATIONAL PROFILING 27Figure
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HUMAN MUTATIONAL PROFILING 29Rieder
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32 SCHMUTZ ET AL.algorithm itself,
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34 SCHMUTZ ET AL.Figure 2. Genomic
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36 SCHMUTZ ET AL.compared. Some of
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Human Subtelomeric DNAH. RIETHMAN,
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HUMAN SUBTELOMERIC SEQUENCES 41The
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HUMAN SUBTELOMERIC SEQUENCES 43cate
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HUMAN SUBTELOMERIC SEQUENCES 45Figu
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HUMAN SUBTELOMERIC SEQUENCES 47pres
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50 COLLINSand expand the genomics r
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52 COLLINSFigure 2. A public-sector
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54 COLLINSdefine all the parts of t
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56 BENTLEYmon over many generations
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58 BENTLEYTable 1. Genetic Disease
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60 BENTLEY(Clark et al. 1998; Reich
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62 BENTLEYACKNOWLEDGMENTSThe author
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SNP Genotyping and Molecular Haplot
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GENETIC ANALYSIS OF DNA POOLS 67gen
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70 FAN ET AL.matrix is then mated t
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72 FAN ET AL.Figure 3. Views of gen
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74 FAN ET AL.including 32 duplicate
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76 FAN ET AL.Figure 7. Allele-speci
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78 FAN ET AL.microsphere-based assa
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80 BERTRANPETIT ET AL.function, may
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82 BERTRANPETIT ET AL.diversity in
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84 BERTRANPETIT ET AL.gree of block
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86 BERTRANPETIT ET AL.Figure 1. Dec
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88 BERTRANPETIT ET AL.1999. Populat
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90 WINDEMUTH ET AL.Expression data.
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92 WINDEMUTH ET AL.Table 1. A Summa
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94 WINDEMUTH ET AL.Table 2. Signifi
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96 WINDEMUTH ET AL.Table 3. Summary
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98 WINDEMUTH ET AL.Table 6. List of
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100 WINDEMUTH ET AL.Table 6. (Conti
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102 WINDEMUTH ET AL.Table 6. (Conti
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104 WINDEMUTH ET AL.much of a surpr
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106 WINDEMUTH ET AL.Given our resul
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Genetic Variation and the Control o
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GENETIC CONTROL OF TRANSCRIPTION 11
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GENETIC CONTROL OF TRANSCRIPTION 11
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Genome-wide Detection and Analysis
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RECENT SEGMENTAL DUPLICATIONS 117Fi
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RECENT SEGMENTAL DUPLICATIONS 119St
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RECENT SEGMENTAL DUPLICATIONS 121Co
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RECENT SEGMENTAL DUPLICATIONS 123Ho
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The Effects of Evolutionary Distanc
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EVOLUTIONARY DISTANCE AND GENE PRED
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EVOLUTIONARY DISTANCE AND GENE PRED
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Lineage-specific Expansion of KRAB
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EVOLUTION OF ZNF GENES 133Figure 2.
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EVOLUTION OF ZNF GENES 135Figure 4.
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EVOLUTION OF ZNF GENES 137get gene,
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EVOLUTION OF ZNF GENES 139Y., Goodw
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Sequence Organization and Functiona
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CENTROMERE ANNOTATION 143THE CENTRO
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CENTROMERE ANNOTATION 145Figure 4.
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CENTROMERE ANNOTATION 147CONCLUSION
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CENTROMERE ANNOTATION 149Schueler M
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152 PARKHILL AND THOMSONFigure 1. T
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154 PARKHILL AND THOMSONshow very h
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156 PARKHILL AND THOMSONGene Loss a
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158 PARKHILL AND THOMSONYersinia ad
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160 MCKAY ET AL.Choosing Candidate
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162 MCKAY ET AL.new comparative too
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164 MCKAY ET AL.rich. Based on a th
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166 MCKAY ET AL.Embryonic Muscle an
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168 MCKAY ET AL.native polyadenylat
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Building Comparative Maps Using 1.5
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HUMAN CHROMOSOME 1p IN THE DOG 1731
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HUMAN CHROMOSOME 1p IN THE DOG 175(
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HUMAN CHROMOSOME 1p IN THE DOG 177l
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180 GEORGES AND ANDERSSON5. There i
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182 GEORGES AND ANDERSSONplied to r
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184 GEORGES AND ANDERSSONbe common
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186 GEORGES AND ANDERSSONin humans
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Evolving Methods for the Assembly o
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ASSEMBLING LARGE GENOMES 191Figure
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ASSEMBLING LARGE GENOMES 193tant ad
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Mouse Genome Encyclopedia ProjectY.
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MOUSE GENOME ENCYCLOPEDIA PROJECT 1
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DNA Sequence Assembly and Multiple
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EULERIAN ASSEMBLY AND MULTIPLE ALIG
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Ensembl: A Genome InfrastructureE.
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ENSEMBL 215projects often submit th
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218 ZHANGthe majority of these are
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220 ZHANGFigure 2. Demonstration of
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222 ZHANG(G.X. Chen et al., in prep
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224 ZHANGWe are waiting for experim
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Ontologies for Biologists: A Commun
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ONTOLOGIES FOR BIOLOGISTS 229al. 20
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ONTOLOGIES FOR BIOLOGISTS 231TOPIC
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ONTOLOGIES FOR BIOLOGISTS 233a.b.Fi
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ONTOLOGIES FOR BIOLOGISTS 2352003.
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238 JOSHI-TOPE ET AL.Figure 1. The
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240 JOSHI-TOPE ET AL.state of knowl
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242 JOSHI-TOPE ET AL.and co-immunop
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The Share of Human Genomic DNA unde
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DNA UNDER SELECTION FROM HUMAN-MOUS
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Detecting Highly Conserved Regions
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DETECTING MULTISPECIES CONSERVED SE
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266 ROE ET AL.noncoding regions. On
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268 ROE ET AL.a48 hpf embryos in Mi
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270 ROE ET AL.aNovel gene KIAA0819[
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272 ROE ET AL.aMouseRatAP00354.2 Hu
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274 ROE ET AL.Tautz D. and Pfeifle
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276 JAILLON ET AL.Detection of Evol
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278 JAILLON ET AL.Table 1. Distribu
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280 JAILLON ET AL.Table 3. Distribu
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282 JAILLON ET AL.ecotig is a resul
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284 OVCHARENKO AND LOOTSdivergent r
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286 OVCHARENKO AND LOOTSmodulation
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288 OVCHARENKO AND LOOTSsequencing
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290 OVCHARENKO AND LOOTSments of cl
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Evolution of Eukaryotic Gene Repert
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EVOLUTION OF EUKARYOTIC GENES AND I
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304 PENNACCHIO, BAROUKH, AND RUBINA
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306 PENNACCHIO, BAROUKH, AND RUBINh
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308 PENNACCHIO, BAROUKH, AND RUBINA
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High-Throughput Mouse Knockouts Pro
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314 FRIDDLE ET AL.screen to lines o
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Identification of Novel Functional
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100 bp ladder68G1168G1168H1168H6100
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FUNCTIONAL ELEMENTS IN HUMAN DNA 32
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High-resolution Human Genome Scanni
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HUMAN GENOME SCANNING 325false-posi
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HUMAN GENOME SCANNING 327affecting
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HUMAN GENOME SCANNING 329methods fo
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332 MALEK ET AL.Figure 1. The bacte
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334 MALEK ET AL.J., Vincent S., and
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336 HARDISON ET AL.reflect blocks o
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338 HARDISON ET AL.plain the region
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340 HARDISON ET AL.CALIBRATION OF T
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342 HARDISON ET AL.PositionRP2.3noE
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344 HARDISON ET AL.cific chromosoma
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346 WESTON ET AL.these differences
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348 WESTON ET AL.els controlled by
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350 WESTON ET AL.ures prominently i
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352 WESTON ET AL.nal and Bop, which
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354 WESTON ET AL.ablp 1466 bopbcrtB
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356 WESTON ET AL.like fold (Fig. 6)
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Implications of Genomics for Public
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GENETIC EPIDEMIOLOGY 361lytic epide
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GENETIC EPIDEMIOLOGY 363curate risk
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A Model System for Identifying Gene
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PTC TASTE GENETICS 367Figure 2. Hap
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PTC TASTE GENETICS 369Table 2. Hapl
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PTC TASTE GENETICS 371the emergence
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374 MCCALLION ET AL.Figure 1. Schem
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Page 390 and 391: Genetics of Schizophrenia and Bipol
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Page 411 and 412: 404 CHEUNG ET AL.netic analysis. Ex
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Page 416 and 417: Regulation of α-Synuclein Expressi
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mtDNA VARIATION 477Figure 8. Temper
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Positive Selection in the Human Gen
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HUMAN-SPECIFIC EVOLUTIONARY CHANGES
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488 UNDERHILLorigin episodes, each
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490 UNDERHILLhaplogroups C through
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492 UNDERHILLO (Fig. 2e) that share
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The New Quantitative BiologyM.V. OL
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NEW QUANTITATIVE BIOLOGY 497alone.
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NEW QUANTITATIVE BIOLOGY 499There w
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NEW QUANTITATIVE BIOLOGY 501ceded,
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