Home » DNA: a brief overview on the reference sequences

DNA: a brief overview on the reference sequences

Share it on:

Human Genome Variation Society (HGVS) nomenclature, the Recommendations for the description of sequence variants in DNA, RNA, and protein sequences, is authorized by the Human Genome Organization (HUGO), under the responsibility of the HGVS Variant Nomenclature Committee (HVNC).

The description of a variant is preceded by the use of a prefix (lowercase letter followed by a period) indicating the type of reference sequence used.

Genomic reference sequence (g.)

The g. prefix denoted linear genomic reference sequence.
It includes all linear DNA molecules.

Coding DNA reference sequence (c.)

Coding DNA reference sequences are denoted by the c. prefix.
The reference sequence includes coding DNA sequence – CDS and and the 5’ and 3’ UTR regions.
The variants are indicated with a “c.” and the first nucleotide of the start codon is considered as position +1. E.g., c.235G>C shows that there has been a substitution of a guanine for a cytosine at position 235 of the coding sequence.
When an intronic variant is to be indicated, the nucleotides of the exons flanking the intron are used as reference points followed by +/- if the variant is after or before the flanking exon, respectively. E.g., c.235+1G>A means that there is a substitution of a guanine for an adenine from the first nucleotide of the splicing donor site of an exon ending at position 235 of the coding sequence; whereas c.345-3A>C means that there is a substitution of an adenine for a cytosine from the third nucleotide of the splicing acceptor site of an exon beginning with the nucleotide at position 345 of the coding sequence. For NC_ or NG_ reference sequences the transcript used should be given in parentheses, e.g., NC_(NM_): c.235+1G>A or NG_(NM_): c.235+1G>A.

Circular genomic reference sequence (o.)

Circular genomic reference sequences are denoted by the o. prefix.
Circular genomic reference sequences comprise for example plasmid sequence.

Mitochondrial reference sequence (m.)

Mitochondrial genomic reference sequences are denoted by the m. prefix.
A mitochondrial reference sequence is a kind of genomic circular reference sequence.
Homo sapiens mitochondrion, complete genome (GenBank NC_012920.1) is the favorite human mtDNA reference sequence.

Non-coding DNA reference sequence (n.)

Non-coding DNA reference sequences are denoted by n. prefix
It includes a transcript of a gene which doesn’t encode a protein.
In a noncoding DNA reference sequence, introns or sequences flanking the gene in 5′ and 3′ are not included, so it cannot be used to provide a description of variants found at the intronic level and upstream and downstream of the gene.

IMPORTANT: Some information inherent in the current consensus of international recommendations has been reported in this brief report. Please consult the guidelines for complete information. Also important to note the words reported on VarNomen: “For additional questions, comments or examples of cases not yet covered, with a suggestion on how to describe them, you can contact VarNomen@HUGO-int.org ” (Find the sites in the bibliography).

Bibliografy