The DNA sequence and comparative analysis of human chromosome 5

Schmutz, Jeremy; Martin, Joel; Terry, Astrid; Couronne, Olivier; Grimwood, Jane; Lowry, State; Gordon, Laurie; Scott, Duncan; Xie, Gary; Huang, Wayne; Hellsten, Uffe; Tran-Gyamfi, Mary Bao; She, Xinwei; Prabhakar, Shyam; Aerts, Andrea; Altherr, Michael R.; Bajorek, Eva; Black, Steve; Branscomb, Elbert; Caoile, Chenier; Challacombe, Jean F.; Chan, Yee Man; Denys, Mirian; Detter, Chris; Escobar, Julio; Flowers, Dave; Fotopulos, Dea; Glavina, Tijana; Gómez, Marı́a; Gonzales, Eidelyn; Goodstenin, David; Grigoriev, Igor V.; Groza, Matthew; Hammon, Nancy; Hawkins, Trevor; Haydu, Lauren E.; Israni, Sanjay; Jett, Jamie; Kadner, Kristen; Kimbal, Heather; Kobayashi, Arthur; Lopez, Frederick; Lou, Yunian; Martínez, Diego; Medina, Catherine; Morgan, Jenna; Nandkeshwar, Richard D.; Noonan, James P.; Pitluck, Sam; Pollard, Martin; Predki, Paul; Priest, James R.; Ramı́rez, Lucı́a; Rash, Sam; Retterer, James; Rodríguez, Álex; Rogers, Stephanie; Salamov, Asaf; Salazar, Angelica; Thayer, Nina; Tice, Hope; Tsai, Ming Jer; Ustaszewska, Anna; Vo, Nu; Wheeler, Jeremy G; Wu, Kevin; Yang, Joan; Dickson, Mark; Cheng, Jan‐Fang; Eichler, Evan E.; Olsen, Anne S.; Pennacchio, Len A.; Rokhsar, Daniel S.; Richardson, Paul; Lucas, Susan; Myers, R; Rubin, Edward M.

doi:10.1038/nature02919

Cited by 114 publications

(92 citation statements)

References 44 publications

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“…Chromosome 5 is one of the largest of the human chromosomes yet has one of the lowest gene densities. 24 A search of the National Center for Biotechnology Information database under the linkage peak region did not reveal any genes that are known to affect MCP-1. However, Schmutz et al 24 analyzed chromosome 5 and observed a high density of conserved non-coding elements in gene poor regions concluding that these regions contain elements that regulate distant genes.…”

Section: Discussionmentioning

confidence: 97%

“…24 A search of the National Center for Biotechnology Information database under the linkage peak region did not reveal any genes that are known to affect MCP-1. However, Schmutz et al 24 analyzed chromosome 5 and observed a high density of conserved non-coding elements in gene poor regions concluding that these regions contain elements that regulate distant genes. Although this region did not meet genome-wide significance, fine mapping of this area is required to exclude this region as influential to MCP-1 levels or to pinpoint a possible gene or regulatory element responsible for the linkage signal.…”

Section: Discussionmentioning

confidence: 97%

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Circulating MCP-1 levels shows linkage to chemokine receptor gene cluster on chromosome 3: the NHLBI Family Heart Study follow-up examination

et al. 2007

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Atherogenesis is a chronic inflammatory process. Critical in the inflammation process is monocyte chemoattractant protein-1 (MCP-1). To locate genomic regions that affect circulating MCP-1 levels, a genome-wide linkage scan was conducted in a sample of whites and blacks. Phenotype and genetic marker data were available for 2501 white and 513 black participants in the National Heart Lung Blood Institute Family Heart Study follow-up examination. Heritability for MCP-1 was 0.37 in whites and 0.47 in blacks after adjusting for the effects of sex, age, age-sex interaction, smoking status, lifetime smoking exposure (pack-years) and field center. Significant linkage was observed for MCP-1 in a combined black and white sample on chromosome 3 (logarithm of the odds ratio (LOD) ¼ 3.5 at 78 cM, P ¼ 0.0001) and suggestive linkage was observed in whites on chromosome 5 (LOD ¼ 1.8 at 128 cM, P ¼ 0.002). Located under the linkage peak on chromosome 3 is the chemokine receptor gene cluster, including CCR2, the receptor for MCP-1. This study provides preliminary evidence linking genetic variation in a receptor to circulating levels of its ligand, as previously demonstrated for the low-density lipoprotein receptor. Further characterization of these chromosomal regions is needed to identify the functional mutations associated with circulating levels of MCP-1.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 97%

Circulating MCP-1 levels shows linkage to chemokine receptor gene cluster on chromosome 3: the NHLBI Family Heart Study follow-up examination

et al. 2007

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“…As described previously, these alternate loci improve read mapping, provide the only reference representation for more than 150 genes, and capture sequence from the 1000 Genomes "decoy" used as a read sink for GRCh37, endowing it with chromosome context (Church et al 2011(Church et al , 2015; The 1000 Genomes Project Consortium 2015). Of particular note, GRCh38 includes 35 different representations for the immune-related leukocyte receptor complex on Chromosome 19 (Pyo et al 2010) and two additional haplotype resolved paths of the highly variable and complex SMN1-containing spinal muscular atrophy (SMA) region on Chromosome 5 (Schmutz et al 2004). The GRC website provides additional information about alternate loci with a series of region-specific pages that provide a graphical display and a report of associated curation issues (https://www.ncbi.nlm.nih.gov/ projects/genome/assembly/grc/human/).…”

Section: Alternate Loci Additionsmentioning

confidence: 99%

Evaluation of GRCh38 and de novo haploid genome assemblies demonstrates the enduring quality of the reference assembly

Graves-Lindsay²,

et al. 2017

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The human reference genome assembly plays a central role in nearly all aspects of today's basic and clinical research. GRCh38 is the first coordinate-changing assembly update since 2009; it reflects the resolution of roughly 1000 issues and encompasses modifications ranging from thousands of single base changes to megabase-scale path reorganizations, gap closures, and localization of previously orphaned sequences. We developed a new approach to sequence generation for targeted base updates and used data from new genome mapping technologies and single haplotype resources to identify and resolve larger assembly issues. For the first time, the reference assembly contains sequence-based representations for the centromeres. We also expanded the number of alternate loci to create a reference that provides a more robust representation of human population variation. We demonstrate that the updates render the reference an improved annotation substrate, alter read alignments in unchanged regions, and impact variant interpretation at clinically relevant loci. We additionally evaluated a collection of new de novo long-read haploid assemblies and conclude that although the new assemblies compare favorably to the reference with respect to continuity, error rate, and gene completeness, the reference still provides the best representation for complex genomic regions and coding sequences. We assert that the collected updates in GRCh38 make the newer assembly a more robust substrate for comprehensive analyses that will promote our understanding of human biology and advance our efforts to improve health.

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“…Humans also have several NAIP genes, only one of which is full length (Schmutz et al, 2004;Romanish et al, 2009). NAIPs are intracellular, cytosolic proteins with a tripartite structure; three N-terminal baculovirus inhibitor of apoptosis (IAP) protein repeat (BIR) domains, a central NACHT domain and C-terminal leucine rich-repeat (LRR) domains.…”

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confidence: 99%