T2T-YAO: A Telomere-to-telomere Assembled Diploid Reference Genome for Han Chinese

Since its initial release in 2001,the human reference genome has undergone continuous improvement in quality,and the recently released telomere-to-telomere(T2T)version-T2T-CHM13—reaches its highest level of continuity and accuracy after 20 years of effort by working on a simplified,nearly homozygous genome of a hydatidiform mole cell line.Here,to provide an authentic complete diploid human genome reference for the Han Chinese,the largest population in the world,we assembled the genome of a male Han Chinese individual,T2T-YAO,which includes T2T assemblies of all the 22+X+M and 22+Y chromosomes in both haploids.The quality of T2T-YAO is much better than those of all currently available diploid assemblies,and its haploid version,T2T-YAO-hp,generated by selecting the better assembly for each autosome,reaches the top quality of fewer than one error per 29.5 Mb,even higher than that of T2T-CHM13.Derived from an individual living in the aboriginal region of the Han population,T2T-YAO shows clear ancestry and potential genetic continuity from the ancient ancestors.Each haplotype of T2TYAO possesses330-Mb exclusive sequences,3100 unique genes,and tens of thousands of nucleotide and structural variations as compared with CHM13,highlighting the necessity of a population-stratified reference genome.The construction of T2T-YAO,an accurate and authentic representative of the Chinese population,would enable precise delineation of genomic variations and advance our understandings in the hereditability of diseases and phenotypes,especially within the context of the unique variations of the Chinese population.

Biliary candidiasis mimicking IgG4-related disease in a patient with normal immunity

Purpose:To report a rare case of biliary candidiasis in a host with normal immunity.Methods:Laboratory tests indicated an elevated G level of 1000 pg/ml.Microscopic examination of pathological sections demonstrated multiple,narrow base,budding yeast cells following Grocott's methenamine silver staining and periodic acid-Schiff staining.Subsequent sequence analysis supported the diagnosis of biliary candidiasis.Results:A 31-year-old previously healthy man developed obstructive jaundice under no obvious inducement.He experienced cholecystectomy and biliary drainage.Surgical specimens revealed granulomatous chronic inflammation in the gallbladder,liver,bile ducts and mesenteric lymph nodes.He was misdiagnosed with tuberculosis and received antituberculosis treatment.However,his condition did not improve.He was finally diagnosed with biliary candidiasis and administered the antifungal treatment with fluconazole.His symptoms improved after such treatment.Conclusions:We reported a case of biliary candidiasis that mimicked IgG4-RD in a host with normal immunity.Our findings highlighted the need for pathological diagnosis in patients with symptoms resembling IgG4-RD.