Literature variant report for CRYL1

In this report you find an overview of the most relevant scientific literature for the relation of gene CRYL1 to hearing loss terms. It includes all abstracts in which variations for this gene have been described.

  • First all the abstracts for CRYL1 are collected based on the occurrence of and its synonyms in MEDLINE abstracts.
  • All abstracts are then ordered based on a 'variation' score. This score is obtained with a TenWise proprietary machine learning algorithm that has been trained for the classification of abstracts that describe genetic variations.
  • All abstracts are then highligted with three types of terms. These represent the genes and its synonyms, terms related to hearing loss and terms related to genetic variation.
A general liteature overview for CRYL1 can be found on the TenWise MLQUERY server.

References
Optimization of simultaneous screening of the main mutations involved in non-syndromic deafness using the TaqMan® OpenArray™ Genotyping platform. Fábio Tadeu Arrojo Martins;Priscila Zonzini Ramos;Maria Carolina Costa Melo Svidnicki;Arthur Menino Castilho;Edi Lúcia Sartorato. 2013. BMC Med Genet. 14. PMID: 24156272

BACKGROUND: Hearing loss is the most common sensory deficit in humans, affecting approximately 10% of the global population. In developed countries, one in every 500 individuals suffers from severe to profound bilateral sensorineural hearing loss. For those up to 5 years old, the proportion is higher, at 2.7 in 1000 individuals, and for adolescents the average is 3.5 in 1000. Among the causes of hearing loss, more than 50% are related to genetic factors. To date, nearly 150 loci and 64 genes have been associated with hearing loss. Mutations in the GJB2 gene, which encodes connexin 26, constitute the main genetic cause. So far, more than 300 variations have been described in this gene.As a response to the clinical and genetic heterogeneity of hearing loss and the importance of correct molecular diagnosis of individuals with hereditary hearing loss, this study worked in the optimization for a diagnostic protocol employing a high-throughput genotyping technology. METHODS: For this work, was used the TaqMan® OpenArray™ Genotyping platform. This is a high performance, high-throughput technology based on real-time PCR, which enables the evaluation of up to 3072 SNPs (Single Nucleotide Polymorphisms), point mutations, small deletions, and insertions, using a single genotyping plate. For the study, were selected the layout allowing to analyze 32 alterations in 96 individuals simultaneously. In the end, the generated results were validated by conventional techniques, as direct sequencing, Multiplex PCR and RFLP-PCR. RESULTS: A total of 376 individuals were analyzed, of which 94 were healthy controls, totaling 4 plates in duplicate. All 31 of the changes analyzed were present in the nuclear genes GJB2, GJB6, CRYL1, TMC1, SLC26A4, miR-96, and OTOF, and in the mitochondrial genes MT-RNR1 and MT-TS1. The reactions were subsequently validated by established techniques (direct sequencing, multiplex PCR, and RFLP-PCR) that had previously been used to perform molecular screening of hearing loss at the Human Genetics Laboratory of the Center for Molecular Biology and Genetic Engineering (CBMEG), at the State University of Campinas (UNICAMP). In total, 11,656 genotyping reactions were performed. Of these, only 351 reactions failed, representing approximately 3.01% of the total. The average accuracy of genotyping using the OpenArray™ plates was 96.99%. CONCLUSIONS: The results demonstrated the accuracy, low cost, and good reproducibility of the technique, indicating that the TaqMan® OpenArray™ Genotyping Platform is a useful and reliable tool for application in molecular diagnostic testing of hearing loss.
Lipid and Alzheimer's disease genes associated with healthy aging and longevity in healthy oldest-old. Lauren C Tindale;Stephen Leach;John J Spinelli;Angela R Brooks-Wilson. 2017. Oncotarget. 8. PMID: 28206976

Several studies have found that long-lived individuals do not appear to carry lower numbers of common disease-associated variants than ordinary people; it has been hypothesized that they may instead carry protective variants. An intriguing type of protective variant is buffering variants that protect against variants that have deleterious effects. We genotyped 18 variants in 15 genes related to longevity or healthy aging that had been previously reported as having a gene-gene interaction or buffering effect. We compared a group of 446 healthy oldest-old 'Super-Seniors' (individuals 85 or older who have never been diagnosed with cancer, cardiovascular disease, dementia, diabetes or major pulmonary disease) to 421 random population-based midlife controls. Cases and controls were of European ancestry. Association tests of individual SNPs showed that Super-Seniors were less likely than controls to carry an APOEε4 allele or a haptoglobin HP2 allele. Interactions between APOE/FOXO3, APOE/CRYL1, and LPA/CRYL1 did not remain significant after multiple testing correction. In a network analysis of the candidate genes, lipid and cholesterol metabolism was a common theme. APOE, HP, and CRYL1 have all been associated with Alzheimer's Disease, the pathology of which involves lipid and cholesterol pathways. Age-related changes in lipid and cholesterol maintenance, particularly in the brain, may be central to healthy aging and longevity.
Genome-wide association interaction analysis for Alzheimer's disease. Elena S Gusareva;Minerva M Carrasquillo;Céline Bellenguez;Elise Cuyvers;Samuel Colon;Neill R Graff-Radford;Ronald C Petersen;Dennis W Dickson;Jestinah M Mahachie John;Kyrylo Bessonov;Christine Van Broeckhoven; ;Denise Harold;Julie Williams;Philippe Amouyel;Kristel Sleegers;Nilüfer Ertekin-Taner;Jean-Charles Lambert;Kristel Van Steen. 2014. Neurobiol Aging. 35. PMID: 24958192

We propose a minimal protocol for exhaustive genome-wide association interaction analysis that involves screening for epistasis over large-scale genomic data combining strengths of different methods and statistical tools. The different steps of this protocol are illustrated on a real-life data application for Alzheimer's disease (AD) (2259 patients and 6017 controls from France). Particularly, in the exhaustive genome-wide epistasis screening we identified AD-associated interacting SNPs-pair from chromosome 6q11.1 (rs6455128, the KHDRBS2 gene) and 13q12.11 (rs7989332, the CRYL1 gene) (p = 0.006, corrected for multiple testing). A replication analysis in the independent AD cohort from Germany (555 patients and 824 controls) confirmed the discovered epistasis signal (p = 0.036). This signal was also supported by a meta-analysis approach in 5 independent AD cohorts that was applied in the context of epistasis for the first time. Transcriptome analysis revealed negative correlation between expression levels of KHDRBS2 and CRYL1 in both the temporal cortex (β = -0.19, p = 0.0006) and cerebellum (β = -0.23, p < 0.0001) brain regions. This is the first time a replicable epistasis associated with AD was identified using a hypothesis free screening approach.
A new large deletion in the DFNB1 locus causes nonsyndromic hearing loss. Delphine Feldmann;Cédric Le Maréchal;Laurence Jonard;Patrick Thierry;Cécile Czajka;Remy Couderc;Claude Ferec;Françoise Denoyelle;Sandrine Marlin;Florence Fellmann. 2008. Eur J Med Genet. 52. PMID: 19101659

Mutations in the GJB2 gene encoding the gap junction protein connexin 26 are responsible for up to 30% of all cases of autosomal recessive nonsyndromic hearing impairment (HI) with prelingual onset in most populations. The corresponding locus DFNB1, located on chromosome 13q11-q12, is also affected by three distinct deletions. These deletions extended distally to GJB2, which remains intact. We report a novel large deletion in DFNB1 observed in a patient presenting profound prelingual HI. This deletion was observed in trans to a GJB2 mutated allele carrying the p.Val84Met (V84M) mutation and was shown to be associated with hearing loss. The deletion caused a false homozygosity of V84M in the proband. Quantification of alleles by quantitative fluorescent multiplex PCR (QFM-PCR) enabled us to study the breakpoints of the deletion. The deleted segment extended through at least 920kb and removed the three connexin genes GJA3, GJB2 and GJB6. The distal breakpoint inside intron 2 of CRYL1 gene differed from the breakpoints of the known DFNB1 deletions. This case highlights the importance of screening for large deletions in molecular studies of GJB2.
Molecular genetic evidence supporting a novel human hepatocellular carcinoma tumor suppressor locus at 13q12.11. Chian-Feng Chen;Shiou-Hwei Yeh;Ding-Shinn Chen;Pei-Jer Chen;Yuh-Shan Jou. 2005. Genes Chromosomes Cancer. 44. PMID: 16075462

A novel 1-cM (1.8 Mb) homozygous deletion (HD) on 13q12.11 was identified in a human hepatocellular carcinoma (HCC) cell line, SK-Hep-1, after high-density genetic marker scan and Southern blotting analysis. A loss of heterozygosity (LOH) analysis indicated that LOH frequency of the HD region in 48 pairs of HCC tissues was 52%. Interestingly, the occurrence of LOH in the 13q12.11 HD region is significantly associated with early-onset HCC, inferred from Fisher's exact test (P = 0.0047) and Mann-Whitney test (P = 0.023). Since the novel 1-cM (1.8 Mb) HD region is gene-rich with more than 37 predicted transcripts, we used a candidate gene approach by examining down-regulation of known tumor suppressor genes (TSGs), including LATS2, TG737, CRYL1, and GJB2, in HCC tissues. We detected only 14% down-regulation of the LAST2 gene that flanks the outside of the HD, in HCC tissues, by quantitative RT-PCR assays. However, we observed significant down-regulation of the TG737, CRYL1, and GJB2 genes located within the HD in 59, 64, and 71% of HCC tissues, respectively. Together, our results indicated that the identified 13q12.11 HD region contained at least three significant down-regulated TSGs, and preferential LOH in early-onset HCC patients is a putative tumor suppressor locus in HCC.
Combined translocation with ZNF198-FGFR1 gene fusion and deletion of potential tumor suppressors in a myeloproliferative disorder. Anne Etienne;Véronique Gelsi-Boyer;Nadine Carbuccia;José Adélaïde;Gianluca Barba;Roberta La Starza;Anne Murati;Virginie Eclache;Françoise Birg;Daniel Birnbaum;Marie-Joëlle Mozziconacci;Christina Mecucci;Max Chaffanet. 2007. Cancer Genet Cytogenet. 173. PMID: 17321332

Tyrosine kinases activated by mutation or translocation are involved in the chronic phase of myeloproliferative disorders. Complementary or alternative events are not so well characterized. We report here a case of t(8;13) generating a ZNF198-FGFR1 fusion kinase gene on the derivative chromosome 13. ZNF198-FGFR1 mRNA, but not FGFR1-ZNF198, was detected by polymerase chain reaction amplification. By using fluorescence in situ hybridization with BAC clones, we mapped a deletion of about 2 megabases on the derivative chromosome 8, including the reciprocal FGFR1-ZNF198 fusion gene and the surrounding genes from 8p11 and 13q12. Potential tumor suppressor genes affected by the deletion by loss (IFT88, CRYL1, TACC1) or break (LATS2) may participate in the malignant process.
Hematopoietic neoplastic diseases develop in C3H/He and C57BL/6 mice after benzene exposure: strain differences in bone marrow tissue responses observed using microarrays. Tohru Inoue;Yoko Hirabayashi. 2009. Chem Biol Interact. 184. PMID: 20018183

In this study, Trp53-deficient and wild-type mice of both C57BL/6 and C3H/He strains were exposed to benzene (33, 100, and 300 ppm; 6h/day, 5 days/week for 26 weeks) and then observed for lifetime. As results, first, the incidence of nonthymic lymphomas in C57BL/6 mice and acute myeloid leukemias (AMLs) in C3H/He mice showed linear responses at the lower exposure level in Trp53-deficient mice; second, the incidence of thymic lymphomas in C57BL/6 mice and nonthymic lymphomas in C3H/He mice increased without a plateau-like ceiling; thus, the former equivocal induction of hematopoietic neoplasms (HPNs) in the case of low-dose benzene exposure was assumed to be based on the DNA repair potential in wild-type mice, and the latter limited increase in HPNs in the case of high-dose benzene exposure was considered to be due to excessive apoptosis in wild-type mice. Concerning the incidence of AMLs, though a dose of 300 ppm benzene inhalation induced 9% AMLs in wild-type C3H/He mice-AML-prone, it induced AMLs in 38% of Trp53-deficient C3H/He mice. Because AMLs were also observed in Trp53-deficient mice, including in the C57BL/6 mice, benzene exposure may also be a potent inducer of AMLs in mice with some strain differences. In the present study, to elucidate the hematopoietic stem cell-specific, aryl hydrocarbon-receptor-related low-dose adverse effect, global gene expression in the bone marrow was analyzed at 28 days after 2-week-intermittent exposure to 150 mg/kg b.w. benzene, by gavage, i.e., equivalent to the above inhalation protocol with 300 ppm. We observed two conceptually different gene expression profiles; "common gene profiles" (CGPs) shared among mice in each group, and "stochastic gene profiles" (SGPs), i.e., unique union genes from one individual mouse to another. The CGPs of the experimental group and the SGPs of each individual mouse were separately characterized by individual assay. Concerning the CGPs, reciprocal strain differences between C3H/He and C57BL/6 mice in expression gene profiles, both plausible for leukemogenesis, were identified; namely, dominant downmodulations of Sltm and Cryl1, related to suppression of apoptosis and genomic instability in C3H/He mice, respectively, and dominant downmodulations of Atrx/rad54 and Kdm2a, related to a decrease in DNA repair and genomic instability, respectively, in C57BL/6 mice. These findings imply that these reciprocal gene expression differences induced by benzene exposure may lead each strain to undergo different hematopoietic neoplastic pathways. In contrast, each individual mouse often shows a unique SGP. SGPs often include transcription factors, which regulate reciprocal signaling pathways including further SGPs. Among them, apoptosis-related genes expressed in C57BL/6 mice and those in C3H/He mice were attributable to different combinations of SGPs. Such stochastic case-by-case gene expression may be in good agreement with the individual and strain differences observed following benzene exposure. Because gene chip microarray techniques can elucidate stochastic changes in gene expression profiles, possible stochastic toxicology and its future role are discussed.
Transcriptome profiling identifies a recurrent CRYL1-IFT88 chimeric transcript in hepatocellular carcinoma. Yi Huang;Jiaying Zheng;Dunyan Chen;Feng Li;Wenbing Wu;Xiaoli Huang;Yanan Wu;Yangyang Deng;Funan Qiu. 2017. Oncotarget. 8. PMID: 28489570

We performed transcriptome sequencing for hepatocellular carcinoma (HCC) and adjacent non-tumorous tissues to investigate the molecular basis of HCC. Nine HCC patients were recruited and differentially expressed genes (DEGs) were identified. Candidate fusion transcripts were also identified. A total of 1943 DEGs were detected, including 690 up-regulated and 1253 down-regulated genes, and enriched in ten pathways including cell cycle, DNA replication, p53, complement and coagulation cascades, etc. Seven candidate fusion genes were detected and CRYL1-IFT88 was successfully validated in the discovery sequencing sample and another 5 tumor samples with the recurrent rate of about 9.52% (6/63). The full length of CRYL1-IFT88 was obtained by 3' and 5' RACE. The function of the fusion transcript is closed to CRYL1 because it contained most of domain of CRYL1. According to the bioinformatics analysis, IFT88, reported as a tumor suppressor, might be seriously depressed in the tumor cell with this fusion because the transcript structure of IFT88 was totally changed. The function depression of IFT88 caused by gene fusion CRYL1-IFT88 might be associated with tumorigenesis or development of HCC.
Reduced CRYL1 expression in hepatocellular carcinoma confers cell growth advantages and correlates with adverse patient prognosis. Ibis K-C Cheng;Arthur K-K Ching;Tsz-Choi Chan;Anthony W-H Chan;Chun-Kwok Wong;Kwong-Wai Choy;Man Kwan;Paul B-S Lai;Nathalie Wong. 2009. J Pathol. 220. PMID: 19927314

Homozygous deletion screening has been widely utilized to define tumour suppressor genes (TSGs) in cancers. Although these biallelic deletions are infrequent, their identification has facilitated the discovery of many important TSGs. We have systematically examined the genome of hepatocellular carcinoma (HCC), a highly malignant tumour that is rapidly fatal, for the presence of homozygous deletions. Array-CGH analysis on early passage of HCC cultures and cell lines led us to identify six homozygous deleted (HD) regions. A high concordance between array-CGH and expression of HD genes was demonstrated, where crystallin Lambda1 (CRYL1; located on chromosome 13q12.11) displayed the most frequent down-regulation. We found that reduced mRNA expression of CRYL1 was common in HCC tumours when compared with their adjacent non-tumoural liver (p = 0.0097). Significant associations could also be drawn between repressed CRYL1 and advanced tumour staging, increased tumour size, and shorter disease-free survival of patients (p < 0.037). Moreover, homozygous deletions on CRYL1 could be detected in 36% of HCC cases, where recurrent HDs were identified on exons 1, 5, and 8. Examination of other causal events suggested histone deacetylation and promoter hypermethylation to be likely inactivating mechanisms as well. Re-expression of CRYL1 in the SK-Hep1 cell line, where biallelic loss of CRYL1 was found, induced profound inhibition of cellular proliferation and cell growth (p < 0.0015). By Annexin V staining, CRYL1 restoration readily increased pro-apoptotic cells with an induction of PARP cleavage. Flow cytometry further revealed that CRYL1 could prolong the G(2)-M phase, possibly through interruption of the Cdc2/cyclin B pathway. Given that regional chromosome 13q12-q14 loss is a causal genomic event in HCC tumourigenesis, our finding may have implications for identifying a novel TSG CRYL1 within this important locus.
Retinoblastoma binding protein 6 and crystallin lambda 1 are cadmium-responsive genes in zebrafish embryos and adults retinae. Rosaria Scudiero;Maria Grazia Esposito;Palma Simoniello;Chiara Maria Motta. 2017. C R Biol. 340. PMID: 28385620

Nonessential metal cadmium is widely used and released in the environment, causing cell toxicity and posing a severe threat to wildlife. Zebrafish (Danio rerio) is one of the most commonly used animals in the investigation of environmental cadmium toxicity in vertebrates. In this study, we identified two cadmium-responsive genes, RBBP6 and CRYL1, in the early phases of zebrafish development, at the gastrula stage. The retinoblastoma binding protein 6 is associated with increased protein degradation and cell proliferation; crystallin-lambda 1 is a lens protein with redox activity. In situ hybridization analysis performed on adult zebrafish exposed to 1.5-40 μM cadmium for 30 days confirmed the ability of cadmium to up-regulate the expression of both genes in retinal cells in a dose-dependent manner. The over-expression was transient, being switched off when cadmium was removed. The involvement of RBBP6 and CRYL1 in the onset of cadmium-induced morphological alterations in adult zebrafish retina is discussed.
Human CRYL1, a novel enzyme-crystallin overexpressed in liver and kidney and downregulated in 58% of liver cancer tissues from 60 Chinese patients, and four new homologs from other mammalians. Jian Chen;Long Yu;Dan Li;Qin Gao;Jishi Wang;Xinghua Huang;Gang Bi;Hai Wu;Shouyuan Zhao. 2003. Gene. 302. PMID: 12527201

Lambda-crystallin is a composition of lens in rabbit and hare. It contains the putative NAD- or FAD-binding domain, which is named as HCDH domain in 3-hydroxyacyl-CoA dehydrogenase. In our attempt to search for genes differentially expressed between liver cancer tissues and normal tissues, human CRYL1 (crystallin, lambda 1) was identified. It was downregulated in 58% of 60 Chinese HCC tissue samples. The putative protein encoded by CRYL1 shares 83% identity with rabbit lambda-crystallin and contains two HCDH domains. Interestingly, CRYL1 mRNA level is remarkably high in liver and kidney, while it is extremely low in peripheral blood leukocyte and thymus. The CRYL1mRNA levels in liver and kidney are about 1.6 and 1.2 times the total amount of that in other 14 tissues, respectively. Both the special expression pattern and the putative HCDH structure of CRYL1 suggested that the protein may be of the similar function of 3-hydroxyacyl-CoA dehydrogenase. To further understand the lambda-crystallin protein family, we cloned four novel mammalian homologs from mouse, rat, bovine and pig. The unrooted phylogenetic tree of this protein family including human and other 26 species was drawn to analyse their evolutionary relationship. In addition, human CRYL1 was mapped to chromosome 13q12.11 and mouse Cryl1 to chromosome 14 between marker D14Mit83 and D14Mit260.
Cloning and characterization of glutamate dehydrogenase (GDH) from the gut of Haemonchus contortus. P J Skuce;E M Stewart;W D Smith;D P Knox. 1999. Parasitology. 118 ( Pt 3). PMID: 10205806

Vaccination of lambs with the membrane-bound (S3) thiol-Sepharose binding protein (TSBP) fraction derived from the gut of Haemonchus contortus confers significant protection against homologous challenge. The S3 TSBP peptide profile is dominated by a major protein of ca. 60 kDa which is strongly recognized by antisera from sheep demonstrably protected following immunization with S3 TSBP. In an attempt to identify this protein, sera from protected lambs were employed to screen a lambda gt11 cDNA library of the adult parasite and resulted in the isolation of numerous clones encoding a homologue of the mitochondrial enzyme, glutamate dehydrogenase (GDH). GDH enzyme activity was readily demonstrable in S3 TSBP material and immunolocalization studies showed that the enzyme was localized to the cytoplasm of the parasite's gut. Furthermore, the enzyme appeared to be developmentally regulated, with both GDH mRNA and protein expressed almost exclusively during the blood-feeding parasitic stages.
Molecular cloning and nucleotide sequence of the cDNA for human liver glutamate dehydrogenase precursor. N Amuro;M Yamaura;Y Goto;T Okazaki. 1988. Biochem Biophys Res Commun. 152. PMID: 3377777

Two cDNA clones (lambda GDHh1 and lambda GDHn61) for glutamate dehydrogenase (GDH) were isolated from a human liver cDNA library in lambda gt11. The clone, lambda GDHh1, was isolated from the library using a synthetic 45mer oligodeoxy-ribonucleotide, the sequence of which was derived from the known amino acid sequence near the NH2-terminus of human liver GDH. Subsequently, lambda GDHn61 was isolated from the same library using lambda GDHh1 as a probe. The inserts of both clones contained an overlapping cDNA sequence for human liver GDH, consisting of a 5'-untranslated region of 70 bp, an open reading frame of 1677 bp, a 3'-untranslated region of 1262 bp and a 15 base poly(A) tract. The predicted amino acid sequence revealed that the human liver GDH precursor consisted of a total of 558 amino acid residues including the NH2-terminal presequence of 53 amino acids. The sequence deduced for the mature enzyme showed 94% homology to the previously reported amino acid sequence of human liver GDH.