Chromosome 19 has the highest gene density of all human chromosomes, more than double the genome-wide average. The large clustered gene families, corresponding high G1C content, CpG islands and density of repetitive DNA indicate a chromosome rich in biological and evolutionary significance. Here we describe 55.8 million base pairs of highly accurate finished sequence representing 99.9% of the euchromatin portion of the chromosome. Manual curation of gene loci reveals 1,461 protein-coding genes and 321 pseudogenes. Among these are genes directly implicated in mendelian disorders, including familial hypercholesterolaemia and insulin-resistant diabetes. Nearly one-quarter of these genes belong to tandemly arranged families, encompassing more than 25% of the chromosome. Comparative analyses show a fascinating picture of conservation and divergence, revealing large blocks of gene orthology with rodents, scattered regions with more recent gene family expansions and deletions, and segments of coding and non-coding conservation with the distant fish species Takifugu.

No abstract

No abstract

No abstract

chow 1* cancer-related mortality of solid tumors remains the major cause of death worldwide. circulating tumor DNA (ctDNA) released from cancer cells harbors specific somatic mutations. Sequencing ctDNA opens opportunities to non-invasive population screening and lays foundations for personalized therapy. in this study, two commercially available platforms, Roche's Avenio ctDNA Expanded panel and QIAgen's QIAseq Human Comprehensive Cancer panel were compared for (1) panel coverage of clinically relevant variants; (2) target enrichment specificity and sequencing performance; (3) the sensitivity; (4) concordance and (5) sequencing coverage using the same human blood sample with ultra-deep next-generation sequencing. Our finding suggests that Avenio detected somatic mutations in common cancers in over 70% of patients while QIAseq covered nearly 90% with a higher average number of variants per patient (Avenio: 3; QIAseq: 8 variants per patient). Both panels demonstrated similar ontarget rate and percentage of reads mapped. However, Avenio had more uniform sequencing coverage across regions with different GC content. Avenio had a higher sensitivity and concordance compared with QIAseq at the same sequencing depth. This study identifies a unique niche for the application of each of the panel and allows the scientific community to make an informed decision on the technologies to meet research or application needs. Cancer is the second leading cause of death worldwide. Cancer-related mortality of most solid tumors remains steady despite intense research on carcinogenesis and significant advancement in effective treatments. It is estimated that 1 in every 6 deaths is related to cancer and late-stage presentation is still very common 1. For cervical and colorectal cancers, population-wide screenings have contributed to the decreasing mortality 2. However, there is still an urgent need for accurate, effective and non-invasive paradigms to reduce cancer-related mortality for other common and deadly cancer types via early diagnosis, personalized therapeutic strategies and disease monitoring. Circulating cell-free DNA (cfDNA) is released into the peripheral blood due to apoptosis, necrosis or active release 3-5. Higher cfDNA level is found in the plasma of cancer patients comparing to healthy controls 6,7. Circulating tumor DNA (ctDNA) from cancer cells harboring a unique set of genetic and epigenetic alterations creates a biological signature. This mutation signature is not only specific to cancer in general when compared to normal tissues but is also highly individual specific 3,8,9. The level of ctDNA, somatic mutations burden, the mutation signature and epigenetic marks are highly correlated with cancer pathophysiology and treatment response 3,10. Unlike traditional biopsy, profiling of somatic mutations via ctDNA is not only minimally invasive but also provides a less localized and biased sampling. Profiling of ctDNA, released from various cells in the tumor, allows a snapshot of somatic mutation burden to provide a more ...