Genomic Medicine and NIH - Francis Collins

Topic:      Genomic Medicine and NIH

Speaker : Francis S Collins, M.D., Ph. D.

                 Director National Institute of Health

Summary:

Medical Science ≠ Clinical Care

• Basic science is the foundation of medical practice but the endeavors demand different approaches

• Theory alone is insufficient to guide action in clinical practice

• The balance between premature translation and inappropriate delay in translation is difficult to achieve

• The stakes are high

• Misapplication regularly results in profound harm

• To patients

• To society through increased cost

• Through missed opportunities

                    

Reference: 

• http://www.youtube.com/GenomeTV

• http://www.genome.gov/27555775

Summary of Current Basic and Extended HGVS Nomenclature Rules at the Genomic DNA Level

Current basic rules in a nutshell^a

1.       Most 3’ position assigned to be changed. Example: g.5delT (not: g.4delT)

2.       Ranges of a reference sequence involved in deletions, duplications or inversions are indicated by their start and end positions separated by an underscore. Example: g.5_10del

3.       The location of an insertion is indicated by the consecutive positions of the flanking nucleotides separated by an underscore. Example: g.5_6insTA

4.       Single variants in multiple alleles are listed separately between square brackets, which are separated by a semicolon. Example: g.[5delT];[123A4G]

5.       Multiple variants in a single allele are listed between square brackets and separated by a semicolon. Example: g.[1A4T; 7del] (not: g.[7del;1A4T])

6.       Variants in a single allele are ordered from 5’ to 3’

Extended rules

1.       ‘‘Suballeles’’ using nested and composite change formats are preferred to describe changes within the range of duplications, inversions, insertions, and gene conversions

2.       Nucleotide numbers or ranges specifying the position of a variant in a suballele refer to the original reference sequence in its original orientation. They cannot exceed the range of the duplication, inversion, or gene conversion to which it belongs

3.       Variants in a suballele are listed between curly braces and separated by a semicolon

4.       When different levels of nesting are used, variant type hierarchy and order are evaluated from the deepest suballele level upward

5.       Sequences inserted in a suballele can be specified by a stretch of nucleotides and/or their corresponding accession number and version number separated by a semicolon and ordered from 5’ to 3’ . Examples: g.5_25dup{11_12insAT}, g.5_2500dup{111_112insAB345678.1} or g.5_2500dup{111_112ins{GC;AB345678.1; AB456789.1;TAC}

6.       Insertions of sequences between 5’ and 3’ copies of a duplicated sequence (i.e., before the start of the 30 copy) have no insertion position numbers in the suballele description. Example: g.5_25dup{insAT}

7.       Multiple variants in a suballele are ordered from 5’ to 3’

^aSee the HGVS guidelines at http://www.hgvs.org/mutnomen/ for the complete set of abbreviations and definitions.

Reference:

Taschner, P.E. & den Dunnen, J.T. Describing structural changes by extending HGVS sequence variation nomenclature. Hum Mutat 32, 507-11 (2011).

Nucleotide Ambiguity Code

Degenerate base symbols in biochemistry are an IUPAC representation for a position on a DNA sequence that can have multiple possible alternatives.

Reference: 

• IUPAC-IUB Commission on Biochemical Nomenclature (CBN). Abbreviations and symbols for nucleic acids, polynucleotides and their constituents. Recommendations 1970. in Biochem J Vol. 120 449-54 (1970).

RefSeq accession format

RefSeq accession numbers and molecule types.

a Whole Genome Shotgun sequence data, b An ordered collection of WGS sequence for a genome, c Computed.

Reference: http://www.ncbi.nlm.nih.gov/books/NBK50679/