Complete genome sequence of the rifamycin SV-producing Amycolatopsis mediterranei U32 revealed its genetic characteristics in phylogeny and metabolism

Amycolatopsis mediterranei is used for industry-scale production of rifamycin, which plays a vital role in antimyco- bacterial therapy. As the first sequenced genome of the genus Amycolatopsis, the chromosome of strain U32 comprising 10 236 715 base pairs, is one of the largest prokaryotic genomes ever sequenced so far. Unlike the linear topology found in streptomycetes, this chromosome is circular, particularly similar to that of Saccharopolyspora erythraea and Nocardia farcinica, representing their close relationship in phylogeny and taxonomy. Although the predicted 9 228 protein-coding genes in the A. mediterranei genome shared the greatest number of orthologs with those of S. erythraea, it was unexpectedly followed by Streptomyces coelicolor rather than N. farcinica, indicating the distinct metabolic characteristics evolved via adaptation to diverse ecological niches. Besides a core region analogous to that common in streptomycetes, a novel ＇quasicore＇ with typical core characteristics is defined within the non-core region, where 21 out of the total 26 gene clusters for secondary metabolite production are located. The rifamycin biosynthesis gene cluster located in the core encodes a cytochrome P450 enzyme essential for the conversion of rifamycin SV to B, revealed by comparing to the highly homologous cluster of the rifamycin B-producing strain S699 and further confirmed by genetic complementation. The genomic information of A. mediterranei demonstrates a metabolic network orchestrated not only for extensive utilization of various carbon sources and inorganic nitrogen compounds but also for effective funneling of metabolic intermediates into the secondary antibiotic synthesis process under the control of a seemingly complex regulatory mechanism.

Metagenome of microorganisms associated with the toxic Cyanobacteria Microcystis aeruginosa analyzed using the 454 sequencing platform

In this study, the 454 pyrosequencing technology was used to analyze the DNA of the Microcystis aeruginosa symbiosis system from cyanobacterial algal blooms in Taihu Lake, China. We generated 183 228 reads with an average length of 248 bp. Running the 454 assembly algorithm over our sequences yielded 22 239 significant contigs. After excluding the M. aeruginosa sequences, we obtained 1 322 assembled contigs longer than 1 000 bp. Taxonomic analysis indicated that four kingdoms were represented in the community: Archaea (n = 9; 0.01%), Bacteria (n = 98 921; 99.6%), Eukaryota (n = 373; 3.7%), and Viruses (n = 18; 0.02%). The bacterial sequences were predominantly Alphaproteobacteria (n = 41 805; 83.3%), Betaproteobacteria (n = 5 254; 10.5%) and Gammaproteobacteria (n = 1 180; 2.4%). Gene annotations and assignment of COG (clusters of orthologous groups) functional categories indicate that a large number of the predicted genes are involved in metabolic, genetic, and environmental information processes. Our results demonstrate the extraordinary diversity of a microbial community in an ectosymbiotic system and further establish the tremendous utility of pyrosequencing.

Evaluation of Four Candidate VNTR Loci for Genotyping 225 Chinese Clinical Mycobacterium Tuberculosis Complex Strains

Objective To evaluate four candidate variable number tandem repeat （VNTR） loci for genotyping Mycobacterium tuberculosis complex strains. Methods Genomic sequences for two M. tuberculosis strains （CCDC5079 and CCDC5180） were generated, and using published sequence data, four candidate VNTR loci were identified. The VNTRs were used to genotype 225 Chinese clinical M. tuberculosis complex strains. The discriminatory power of the VNTRs was evaluated using BioNumerics 5.0 software. Results The Hunter-Gaston Index （HGI） for BJ1, BJ2, BJ3, and BJ4 loci was 0.634, 0.917, 0.697, and 0.910, respectively. Combining all four loci gave an HGI value of 0.995, thus confirming that the genotyping had good discriminatory power. The HGI values for BJ1, BJ2, BJ3, and BJ4, obtained from Beijing family strain genotyping, were 0.447, 0.878, 0.315, and 0.850, respectively. Combining all four loci produced an HGI value of 0.988 for genotyping the Beijing family strains. We observed unique patterns for M. boris and M. africanum strains from the four loci. Conclusion We have shown that the four VNTR loci can be successfully used for genotyping M. tuberculosis complex strains. Notably, these new loci may provide additional information about Chinese M. tuberculosis isolates than that currently afforded by established VNTR loci typing.

Polymorphisms of TLR7 and TLR8 associated with risk of asthma and asthma-related phenotypes in a southeastern Chinese Han population

Objective： To evaluate the effects of polymorphisms in TLR7 and TLRS（as potential candidate genes） on asthma risk and asthma-related phenotypes. Methods： We consecutively recruited 318 unrelated adult asthmatic patients and 352 healthy volunteers from the same area of southeast China. Genotyping of each selected SNP was performed using multiplex PCR in conjunction with tagged array single base extension technology. We conducted case-control and case-only association studies between the selected SNPs in TLR7 and TLR8 and asthma or asthma-related phenotypes. Results： The T allele of rs5935436 SNP in TLR7 was protective from developing asthma in males （adjusted ORs = 0.126, 95% CIs = 0.016-0.995）. The CT/TT genotype of rs5935436 was less frequent in female asthmatics with allergic rhinitis （adjusted ORs = 0.18, 95% CIs = 0.04-0.90）. The homozygote AA of rs3761623 and GG of rs3764880 were positively associated with lower FEV1% and asthma severity in female asthmatics. These results were confirmed by haplotype analysis. Conclusion：TLR7 and TLR8 polymorphisms may play an important role in the pathogenesis of asthma that is gender-dependent. This could be clinically useful, both for identifying patients at risk of asthma and for preventing its occurrence.

Diagnostic and economic value of carcinoembryonic antigen,carbohydrate antigen 19-9,and carbohydrate antigen 72-4 in gastrointestinal cancers

BACKGROUND The diagnostic and economic value of carcinoembryonic antigen(CEA),carbohydrate antigen 19-9(CA19-9)and CA72-4 for gastrointestinal malignant tumors lacked evaluation in a larger scale.AIM To reassess the diagnostic and economic value of the three tumor biomarkers.METHODS A retrospective analysis of all 32857 subjects who underwent CEA,CA19-9,CA72-4,gastroscopy and colonoscopy from October 2006 to May 2018 was conducted.Then,we assessed the discrimination and clinical usefulness.Total cost,cost per capita and cost-effectiveness ratios were used to evaluate the economic value of two schemes(gastrointestinal endoscopy for all people without blood tests vs both gastroscopy and colonoscopy when blood tests were positive).RESULTS The analysis of 32857 subjects showed that CEA was a qualified biomarker for colorectal cancer(CRC),while the diagnostic efficiencies of CA72-4 were catastrophic for all gastrointestinal cancers(GICs).Regarding early diagnosis,only CEA could be used for early CRC.The combination of biomarkers didn’t greatly increase the area under the curve.The economic indicators of CEA were superior to those of CA19-9,CA72-4 and any combination.At the threshold of 1.8μg/L to 10.4μg/L,all four indicators of CEA were lower than those in the scheme that conducted gastrointestinal endoscopy only.Subgroup analysis implied that the health checkup of CEA for people above 65 years old was economically valuable.CONCLUSION CEA had qualified diagnostic value for CRC and superior economic value for GICs,especially for elderly health checkup subjects.CA72-4 was not suitable as a diagnostic biomarker.

NOVEL SPLICING MUTATION OF COL1A1 GENE CAUSING OSTEOGENESIS IMPERFECTA TYPE I IN CHINESE PEDIGREE

Objective To detect the peculiar mutation in a Chinese family with osteogenesis imperfecta, COL1A1 and COL1A2 being analysed. Methods A genome screen was undertaken covering COL1A1 at 17q21- 22 and COLIA2 at 7q22.1. The Linkage （ Version 5. 1 ） was used for 2-point analysis. DNA sequencing was used to screen and identify the mutation. Results A linkage to the markers on chromosome 17q21-22 was observed. Se- quence analysis of COLIA1 revealed a splicing mutation （IVSS-2A 〉 G） that converted the 3＇ end of intron 8 from AG to GG. Conclusion This mutation （ IVS 8-2A 〉 G） is novel, and has not yet been registered in the Human Type I and Type Ⅲ Collagen Mutations Database.

Genetic aberration in primary hepatocellular carcinoma:correlation between p53 gene mutation and loss-of-heterozygosity on chromosome 16q21-q23 and 9p21-p23

To elucidate the molecular pathology underlying the development of hepatocellular carcinoma (HCC), we used 41 highly polymorphic microsatellite markers to examine 55 HCC and corresponding non-tumor liver tissues on chromosome 9, 16 and 17. Loss-of-heterozygosity (LOH) is observed with high frequency on chromosomal region 17p13 (36/55, 65%), 9p21-p23 (28/55, 51%), 16q21-q23 (27/55, 49%) in tumors. Meanwhile, microsatellite instability is rarely found in these microsatellite loci. Direct sequencing was performed to detect the tentative mutation of tumor suppressor genes in these regions: p53, MTS1/p16, and CDH1/E-cadherin. Within exon 5-9 of p53 gene, 14 out of 55 HCC specimens (24%) have somatic mutations, and nucleotide deletion of this gene is reported in HCC for the first time. Mutation in MTS1/pl6 is found only in one tumor case. We do not find mutations in CDH1/E-cadherin. Furthermore, a statistically significant correlation is present between p53 gene mutation and loss of chromosome region 16q21q23 and 9p21-p23, which indicates that synergism between p53 inactivation and deletion of 16q21-q23 and 9p21-p23 may play a role in the pathogenesis of HCC. Genetic aberration in hepatocellular

A case-control study of the relationship between hepatitis B virus DNA level and risk of hepatocellular carcinoma in Qidong,China

AIM:To investigate the role of hepatitis B virus (HBV) replication in the development of hepatocellular carcinoma (HCC), a nested case-control study was performed to study the relationship between HBV DNA level and risk of HCC. METHODS:One hundred and seventy cases of HCC and 276 control subjects free of HCC and cirrhosis were selected for this study. Serum HBV DNA level was measured using fluorescein quantitative polymerase chain reaction at study entry and the last visit. RESULTS:In a binary unconditional logistic regression analysis adjusted for age, cigarette smoking, alcohol consumption and family history of chronic liver diseases, the adjusted odds ratios (95% confidence intervals) of HCC in patients with increasing HBV DNA level were 2.834 (1.237-6.492), 48.403 (14.392-162.789), 42.252 (14.784-120.750), and 14.819 (6.992-31.411) for HBV DNA levels ≥ 104 to < 105; ≥ 105 to < 106; ≥ 106 to < 107; ≥ 107 copies/mL, respectively. Forty-six HCC cases were selected to compare the serums viral loads of HBV DNA at study entry with those at the last visit. The HBV DNA levels measured at the two time points did not differ significantly.CONCLUSION:The findings of this study provide strong longitudinal evidence of an increased risk of HCC associated with persistent elevation of serum HBV DNA level in the 104-107 range.

High-coverage proteome analysis reveals the first insight of protein modification systems in the pathogenic spirochete Leptospira interrogans

Leptospirosis is a widespread zoonotic disease caused by pathogenic spirochetes of the genus Leptospira that infects humans and a wide range of animals. By combining computational prediction and high-accuracy tandem mass spectra, we revised the genome annotation of Leptospira interrogans serovar Lai, a free-living pathogenic spirochete responsible for leptospirosis, providing substantial peptide evidence for novel genes and new gene boundaries. Subsequently, we presented a high-coverage proteome analysis of protein expression and multiple posttranslational modifications （PTMs）. Approximately 64.3% of the predicted L. interrogans proteins were cataloged by detecting 2 540 proteins. Meanwhile, a profile of multiple PTMs was concurrently established, containing in total 32 phosphorylated, 46 acetylated and 155 methylated proteins. The PTM systems in the serovar Lai show unique features. Unique eukaryotic-like features of L. interrogans protein modifications were demonstrated in both phosphorylation and arginine methylation. This systematic analysis provides not only comprehensive information of high-coverage protein expression and multiple modifications in prokaryotes but also a view suggesting that the evolutionarily primitive L. interrogans shares significant similarities in protein modification systems with eukaryotes.

Assessment of Prognostic Factors of Racial Disparities in Testicular Germ Cell Tumor Survival in the United States(1992–2015)

Objective Testicular germ cell tumors(TGCT) are the most common cancer among men aged 15 to 39 years. Previous studies have considered factors related to TGCT survival rate and race/ethnicity, but histological type of the diagnosed cancer has not yet been thoroughly assessed.Methods The data came from 42,854 eligible patients from 1992 to 2015 in the Surveillance Epidemiology and End Results 18. Frequencies and column percent by seminoma and nonseminoma subtypes were determined for each covariates. We used Cox proportional hazard regression to assess the impact of multiple factors on post-diagnostic mortality of TGCT.Results Black males were diagnosed at a later stage, more commonly with local or distant metastases.The incidence of TGCT in black non-seminoma tumors increased most significantly. The difference in survival rates between different ethnic and histological subtypes, overall survival(OS) in patients with non-seminoma was significantly worse than in patients with seminoma. The most important quantitative predictor of death was the stage at the time of diagnosis, and older diagnostic age is also important factor affecting mortality.Conclusion Histological type of testicular germ cell tumor is an important factor in determining the prognosis of testicular cancer in males of different ethnic groups.

MicroRNAs as potential biomarkers for gastric cancer

Gastric cancer is the fourth most common cancer in the world and the second leading cause of cancer-related death. More than 80% of diagnoses occur at the middle to late stage of the disease, highlighting an urgent need for novel biomarkers detectable at earlier stages. Recently, aberrantly expressed microRNAs (miRNAs) have received a great deal of attention as potential sensitive and accurate biomarkers for cancer diagnosis and prognosis. This review summarizes the current knowledge about potential miRNA biomarkers for gastric cancer that have been reported in the publicly available literature between 2008 and 2013. Available evidence indicates that aberrantly expressed miRNAs in gastric cancer correlate with tumorigenesis, tumor proliferation, distant metastasis and invasion. Furthermore, tissue and cancer types can be classified using miRNA expression profiles and next-generation sequencing. As miRNAs in plasma/serum are well protected from RNases, they remain stable under harsh conditions. Thus, potential functions of these circulating miRNAs can be deduced and may implicate their diagnostic value in cancer detection. Circulating miRNAs, as well as tissue miRNAs, may allow for the detection of gastric cancer at an early stage, prediction of prognosis, and monitoring of recurrence and/or lymph node metastasis. Taken together, the data suggest that the participation of miRNAs in biomarker development will enhance the sensitivity and specificity of diagnostic and prognostic tests for gastric cancer. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

The localization of type 2 diabetes susceptibility gene loci in northern Chinese Han families

We conducted a genome-wide scan, in which 358 well distributed fluorescent dye-labeled microsatellite marker sets were applied in 32 Chinese Han type 2 diabetes families from Northern China to search for the susceptibility gene loci. The data collected from screening all the chromosomes of genome were genotyped by using genescan and genotyping software, then, parametric and non-parametric multipoint test, and affected sib-pair analysis as well, were used to analyze the data. We identified some susceptibility gene loci residing in chromosomes 1,12,18,20, respectively, or precisely, located around D1S214, D1S207, D1S218, D1S235, D12S336, D18S61 and D20S118. The comparison of this result with those from other regions and races reflected the complexity and heterogeneity of type 2 diabetes.

“Beijing Region” (3pter-D3S3397) of the Human Genome: Complete sequence and analysis

The goal of the Human Genome Project (HGP) is to determine a complete and high-quality sequence of the human genome. China, as one of the six member states, takes a region between 3pter and D3S3397 of the human chromosome 3 as its share of this historic project, referred as “Beijing Region”. The complete sequence of this region comprises of 17.4 megabasepairs (Mb) with an average GC content of 42% and an average recombination rate of 2.14 cM/Mb. Within Beijing Region, 122 known and 20 novel genes are identified, as well as 42607 single nucleotide polymorphisms (SNPs). Comprehensive analyses also reveal: (i) gene density and GC-content of Beijing Region are in agreement with human cytogenetic maps, i.e. G-minus bands are GC-rich and of a high gene density, whereas G-plus bands are GC-poor and of a relatively low gene density; (ii) the average recombination rate within Beijing Region is rela-tively high compared with other regions of chromosome 3, with the highest recombination rate of 6.06 cM/Mb in the subtelomeric area; (iii) it is most likely that a large gene, associated with the mammary gland, may reside in the 1.1 Mb gene-poor area near the telomere; (iv) many dis-ease-related genes are genetically mapped to Beijing Region, including those associated with cancers and metabolic syndromes. All make Beijing Region an important target for in-depth mo-lecular investigations with a purpose of medical applications.

Fine genetic mapping of the chromosome 11q23.3 region in a Han Chinese population:insights into the apolipoprotein genes underlying the blood lipid-lipoprotein variances

The unusual chromosome 11q23.3 harboring the apolipoprotein(APO)gene cluster has been well documented for its essential roles in plasma lipid-related traits and atherosclerotic cardiovascular diseases.However,its genetic architecture and the potential biological mechanisms underlying complex phenotypes have not been well assessed.We conducted a study for this target region in a Han Chinese population through a stepwise forward framework based on massive parallel sequencing,association analyses,genetic fine mapping,and functional interpretation.The present study identified new meaningful genetic associations that were not simply determined by statistical significance.In addition to the APOA5 gene,we found robust evidence of the genetic commitments of APOC3 and APOA1 to blood lipids.Several variants with high confidence were prioritized along with the potential biological mechanism interpretations in the wake of adaptive fine-mapping analyses.rs2849174 in the APOC3 enhancer was discovered with an unrivaled posterior probability of causality for triglyceride levels and could mediate APOC3 expression through enhancer activity modulated by a combination of histone modifications and transcription factor accessibility.Similarly,multiple lines of evidence converged in favor of rs3741297 as a causal variant influencing high-density lipoprotein cholesterol.Our findings provided novel insights into this genomic locus in the Chinese population.

Amino Acid Biosynthesis and Proteolysis in <i>Lactobacillus Bulgaricus</i>Revisited: A Genomic Comparison

The amino acid biosynthesis and proteolytic system of Lactobacillus bulgaricus (L.Bulgaricus ) is important for its growth in niche-specific environments, as well as for flavour formation in the food industry. Comparative analyses of 4 completed sequences of the L.Bulgaricus strain genome on a genomic scale revealed that genes involved in amino acids synthesis were undergoing reductive evolution. However, the selected industrial strains, namely, L.Bulgaricus 2038 and L.Bulgaricus ND02, retained more complete genes in the amino acid synthesis and proteolytic system category than the laboratory strains, and have some unique genes and pathways for obtaining amino acids that enable these bacteria to adapt to their various environmental niches.

A systematic study of the whole genome sequence of Amycolatopsis methanolica strain 239T provides an insight into its physiological and taxonomic properties which correlate with its position in the genus

The complete genome of methanol-utilizing Amycolatopsis methanolica strain 239T was generated,revealing a single 7,237,391 nucleotide circular chromosome with 7074 annotated protein-coding sequences(CDSs).Comparative analyses against the complete genome sequences of Amycolatopsis japonica strain MG417-CF17T,Amycolatopsis mediterranei strain U32 and Amycolatopsis orientalis strain HCCB10007 revealed a broad spectrum of genomic structures,including various genome sizes,core/quasi-core/non-core configurations and different kinds of episomes.Although polyketide synthase gene clusters were absent from the A.methanolica genome,12 gene clusters related to the biosynthesis of other specialized(secondary)metabolites were identified.Complete pathways attributable to the facultative methylotrophic physiology of A.methanolica strain 239T,including both the mdo/mscR encoded methanol oxidation and the hps/hpi encoded formaldehyde assimilation via the ribulose monophosphate cycle,were identified together with evidence that the latter might be the result of horizontal gene transfer.Phylogenetic analyses based on 16S rDNA or orthologues of AMETH_3452,a novel actinobacterial class-specific conserved gene against 62 or 18 Amycolatopsis type strains,respectively,revealed three major phyletic lineages,namely the mesophilic or moderately thermophilic A.orientalis subclade(AOS),the mesophilic Amycolatopsis taiwanensis subclade(ATS)and the thermophilic A.methanolica subclade(AMS).The distinct growth temperatures of members of the subclades correlated with corresponding genetic variations in their encoded compatible solutes.This study shows the value of integrating conventional taxonomic with whole genome sequence data.

ASSOCIATION ANALYSIS OF POLYMORPHISMS IN SIX GENES WITHIN THE GH/IGF-1 AXIS IN PATIENTS WITH IDIOPATHIC SHORT STATURE IN THE CHINESE HAN POPULATION

Objective To investigate relationships of polymorphisms in six genes （ GHR, IGF-1, IGF-1R, IGFBP-3, JAK2, and STAT5b） in the growth hormone （GH）/insulin-like growth factor-1 （IGF-1） axis with idiopathic short stature （ISS） in the Chinese Han population. Methods A case- control study was carried out on a cohort of 198 ISS patients and 306 healthy controls. A total of 106 tagging single nucleotide polymorphisms （tagSNPs） from the six genes were selected from the HapMap （haplotype map of the human genome ） Han Chinese in the Beijing subset. Results of genotyping conducted by high- throughput lllumina GoldenGateTM Assay were analyzed by statistical software. Results Both individual tagSNPs and haplotypes showed an association with 1SS in the Han Chinese population （ P 〈 O. 05 ）. For each single test, both allele and genotype were tested. By allele frequency analysis, six positive SNP sites （ rsNo. 1, rsNo. 2, rsNo. 3, rsNo. 4, rsNo. 5, and rsNo. 6） of 3 genes （ JAK2, 1GF-1R, and GHR） were found having associations with ISS. By genotype frequency analysis, there were significant differences between the patient and control groups in the following SNP sites： 4 sites in JAK2 gene （ rsNo. 1, rsNo. 2, rsNo. 3, and rsNo. 4） and 1 site in GHR gene （ rsNo. 6）. The risk which affected ISS was found related to the JAK2 gene in 4 sites （ increase in rsNo. 1 and decrease in rsNo. 2, rsNo. 3, and rsNo. 4 ） and to the GHR gene in 1 site （decrease in rsNo. 6）. They were four haplotypes in gene of IGF-1R as ＂TGC＂, ＂CGCT＂, ＂TA＂, and ＂ CA＂, one haplotype in IGFBP-3 as ＂TA＂, and one haplotype in JAK2 as ＂CTG＂, which revealed high significance for risks of affecting ISS. At last, multivariate logistic regression analysis of specific site rsNo. 6 of the GHR gene revealed that the serum IGF-1 was related to genotypes AA and AC, with genotype CC as the reference （ P =0. 015）. Conclusion Genetic variances in six genes within the GH/IGF-1 axis may be important etiological factors for ISS in the Chinese Han population.

Bioinformatic analysis of human nuclear receptor nr5a2(hb1f) genomic sequence

We have cloned the cDNA of human nuclear receptor nr5a2(hb1f) gene and obtained its whole genomic sequence previously. In this work we carried out in-depth bioinformatic analysis on the genomic sequence of nr5a2(hb1f) gene. Sequence comparison and prediction algorithms implicated that there might be additional coding regions in the 210 kb genomic sequence besides known exons, especially in the two largest introns. Comparison of the structures of nr5a loci in different species revealed distinguishable conservation and apparent gene duplication during evolution. The remarkable conservation among promoters of zebrafish, mouse and human nr5a2 genes suggested that they would be regulated by the same transcription factors.

Insights into the Bamboo Genome:Syntenic Relationships to Rice and Sorghum

Bamboo occupies an important phylogenetic node in the grass family and plays a significant role in the forest industry.We produced 1.2 Mb of tetraploid moso bamboo （Phyllostachys pubescens E.Mazel ex H.de Leh.） sequences from 13 bacterial artificial chromosome （BAC） clones,and these are the largest genomic sequences available so far from the subfamily Bambusoideae.The content of repetitive elements （36.2%） in bamboo is similar to that in rice.Both rice and sorghum exhibit high genomic synteny with bamboo,which suggests that rice and sorghum may be useful as models for decoding Bambusoideae genomes.

Autosomal dominant coralliform cataract related to a missense mutation of the γD-crystallin gene

Background Congenital cataract is a sight-threatening disease that affects about 1-6 cases per 10000 live births and causes 10%-30% of all blindness in children About 25% of all cases are due to genetic defects We identified autosomal dominant congenital coralliform cataracts-related genetic defect in a four-generation Chinese family Methods Complete ophthalmological examinations were performed prior to lens extraction Lens samples were then studied by electron microscopy Genomic DNA from family members were examined using whole-genomic linkage analysis, with two-point logarithm of odds (LOD) scores calculated using the Linkage program package (version 5 1) Mutation analysis of candidate genes was performed by direct sequencing Finally, a three-dimensional protein model was predicted using Swiss-Model (version 2 0) Results Eleven of the 23 examined individuals had congenital cataracts Ultrastructure studies revealed crystal deposits in the lens, and granules extensively dispersed in transformed lens fiber cells The maximum two-point LOD score, 3 5 at θ=0 1, was obtained for the marker D2S325 Mutation analysis of the γ-crystallin (CRYG) gene cluster identified a mutation (P23T) in exon 2 of γD-crystallin (CRYGD) Protein structure modeling demonstrated that the P23T mutation caused a subtle change on the surface of the γD protein Conclusions The results suggest that the coralliform cataract phenotype is due to a mutated CRYGD gene, and that this sequence change is identical to one reported by Santhiya to be related to another distinct clinical condition, lamellar cataract This study provides evidence that this same genetic defect may be associated with a different phenotype This is the first report identifying the genetic defect associated with an autosomal dominant congenital coralliform cataract