Human & Mouse Orthologous Gene Nomenclature (HUMOT) HUGO Gene Nomenclature Committee (HGNC) Matt Wright

The Role of HGNC Assign unique approved gene names and symbols Assign unique approved gene names and symbols Co-ordinate with other databases and nomenclature groups Co-ordinate with other databases and nomenclature groups Collate and curate data (Genew) Collate and curate data (Genew)

Searchgenes

Gene Symbol Report

Why Use Approved Nomenclature? Standardisation Standardisation User friendly User friendly Communication Communication Manually curated Manually curated Consistency across species Consistency across species

Naming Criteria Stable MeaningfulMemorable Unique

Symbol Assignment Sequence comparison Sequence comparison Information from literature Information from literature Information from researchers Information from researchers Domain structures Domain structures Information from other databases Information from other databases

HUMOT Two dedicated HUMOT editors Approve the same gene symbol for each human/mouse ortholog pair Human gene symbols are written in all uppercase letters (e.g. human PON3) Mouse only the first letter is uppercase and the rest are lowercase (e.g. mouse Pon3).

Definitions Orthologs Orthologs Related by speciation (and preferably by function) Paralogs Paralogs Related by gene duplication Mouse Gene Rat Gene Human Gene 1 Human Gene 2 Common Ancestral Gene

Determining Orthology Best BLAST hit, Reciprocal BLAST Best BLAST hit, Reciprocal BLAST with approved symbol PON3

BLAST Problems Unequal rates of evolution Unequal rates of evolution Hidden paralogy Hidden paralogy Large numbers of genomes Large numbers of genomes Mouse Gene 1 Mouse Gene 2 Human Gene Rat Gene 2 Mouse Gene 2 Human Gene 2 Rat Gene 1 Mouse Gene 1 Human Gene 1 Unequal rates Hidden paralogy

Determining Orthology Best BLAST hit, Reciprocal BLAST Best BLAST hit, Reciprocal BLAST Conserved Synteny Conserved Synteny

Conserved Synteny HUMAN MOUSE (taken from doegenomes.org)

Conserved Synteny Human Symbol PON1 PON2 PON3 Mouse Symbol Pon1 Pon2 Pon3 Human Location 7q21.3 Mouse Location 6 A2 6 A1 Searched with approved symbol PON2

Determining Orthology Best BLAST hit, Reciprocal BLAST Best BLAST hit, Reciprocal BLAST Conserved Synteny Conserved Synteny Phylogeny Phylogeny

Phylogeny PON1 PON2 PON3 Searched with approved symbol PON1

Orthology Resources Provider HGNC: MGI: NCBI: Ensembl: JGI: ANGIS: Resource HUMOT Consensus Orthology Search Mammalian Orthology Query Oxford Grid Comparative Maps Human/Mouse Orthology Map Homologene MapViewer ‘Orthologue Predictions’ in Ensembl gene reports PhIGs Search PhIGs Synteny Viewer Oxford Grid

Consensus Orthology Search HGNC, MGI, Homologene, Ensembl and PhIGs orthology assertions Will include approved symbols and names, DNA sequences, database identifiers, aliases, and chromosomal locations for each putative ortholog pair.

Determining Orthology Best BLAST hit, Reciprocal BLAST Best BLAST hit, Reciprocal BLAST Conserved Synteny Conserved Synteny Phylogeny Phylogeny Orthology Resources Orthology Resources WE DO NOT MAKE AN ORTHOLOGOUS ASSERTION IF RESULTS ARE UNCLEAR WE DO NOT MAKE AN ORTHOLOGOUS ASSERTION IF RESULTS ARE UNCLEAR

HGNC HUMOT Activities 2,500 curated orthology assertions 7,000 consensus orthology assertions Examine human/mouse orthologs with different approved symbols Eradicating mis-mapped data

MGI Oxford Grid A section from the MGI Oxford Grid (September 2004) mouse chromosomes humanhuman 270 mouse chromosome 6 genes with orthologs on human chromosome 7

humanhuman mouse chromosomes Oxford Grid Singletons A section from the MGI Oxford Grid (April 2005) 279 mouse chromosome 6 genes with orthologs on human chromosome 7

Future Work Continue to assign orthologous gene nomenclature Provide common nomenclature for human/mouse orthologs with different symbols Utilise the large cDNA data sets such as those from the H-Invitational and RIKEN to rapidly identify and assign parallel nomenclature

cDNA Data Sets Gene structures Secondary/Tertiary Structure Possible functions Encoded functional domains Sub-cellular localizations Sub-cellular localizations

HGNC Team Dr Varsha Khodiyar Conover Talbot Jr. Fabrice Ducluzeau Prof Sue Povey (Chair) Dr Elspeth Bruford (Project Co-ordinator) Dr Matt Wright (HUMOT Editor) Dr Ruth Lovering (HUGOA Editor) Dr Michael Lush The work of the HGNC is supported by the Wellcome Trust, NHGRI grant P41 HG and the UK Medical Research Council. (Senior Bioinformatician) Dr Tam Sneddon Dr Tina Eyre Dr Kate Sneddon