NO019.20190116.NAR.Locus Reference Genomic: reference sequences for the reporting of clinically r...

原文链接：Locus Reference Genomic: reference sequences for the reporting of clinically relevant sequence variants

原文摘录：

1. Accurate and unambiguous annotation of disease-causing variants is essential. Central to this is the reference DNA sequence with respect to which a variant is reported.
2. Specifically designed for the reporting of diagnostically relevant variants, an LRG provides a stable reference sequence record for a particular genomic locus: genomic DNA, transcript and protein sequences are all included in one record, thereby providing a concise ‘one-stop’ record for variant reporting in all coordinates.（一条记录同时包含基因组DNA序列、转录本序列以及蛋白序列）
3. The sequences defined by an LRG accession will never change.（LRG中的ID永不改变）
4. Mapping of the LRG to current and previous genome assemblies is included in the LRG record, thus overcoming difficulties for the user associated with updates to the genome assembly.（LRG序列与基因组的比对信息也被收录在了LRG记录中）
5. LRG records are created in response to requests from members of the community.（先提出需求，然后才创建记录）
6. Any collaborators with significant involvement in the selection of reference sequences for inclusion in the LRG are asked if they would like to be added as an additional requester.（不断扩大requester数量，以方便更多需求的提出，以完善LRG）
7. Most LRG genomic sequences extend 5 kb upstream of the first exon and 2 kb downstream of the last exon, or to the extent necessary to cover all relevant components (i.e. promoters or other regulatory elements).
8. poly-A tails are removed from all LRG transcripts.
9. 每一个LRG序列都有对应的相应版本的RefSeq和RefSeqGene序列，如果待创建的LRG序列没有对应的RefSeq序列的话，根据请求，RefSeq Curators会先创建该序列，然后LRG再创建！因此，LRG序列与RefSeq之间的变异坐标转换是非常简单的！
10. Currently, all LRGs created have been for genic loci; however, they can be created for any locus with clinical implications.
11. As the project aims to reduce ambiguity, only transcripts that are well characterized and are deemed by the community to be essential for variant reporting are included. In practice this means that the majority of LRGs only have one transcript.（标准严苛，不轻易放行）
12. In rare cases, the collaborators have requested to use an idealized transcript, for example, containing all exons of the gene, as the reporting standard, even though the existence of such a transcript is not supported by biological evidence. Examples of such cases are described in the Supplementary Data. In such cases, the proposed sequences are also reviewed by RefSeq curators and a corresponding RefSeq transcript created.（对其中一种特殊情况的阐述：还是要先经过RefSeq的review，审核通过并添加了相应的转录本后，才会在LRG中添加该转录本）
13. The long-term goal of the LRG project is to create an LRG record for every clinically relevant locus.
14. HGVS-compliant variant descriptions based on the LRG will be added to ClinVar to support searching and reporting.
15. Should the need arise in the future to create multiple LRGs for the same locus, these will have different accession numbers, rather than versions of the same accession number. Therefore, this will eliminate the ambiguity caused by versioning in variant reporting.（不同的ID，而不是相同ID的不同version）
16. Once the review process is complete, a pending LRG is made public and requesters are notified. From this point, sequences included in the fixed section will not change. Additional transcripts can be added to the fixed section of a public LRG in the future should this be necessary for reporting variants at the locus.（一旦状态由pending更新为public之后，fixed部分的信息将不允许被修改。但是由于报告变异的需要而新增新的转录本，这是允许的！）
17. LRGs are established to provide a consistent reporting framework. Because of this policy, should an error in an LRG sequence be identified after release, the sequence in the LRG will not be changed.（这句话每台读懂，是不是说除非发现了错误，否则序列不会改变？）