Publications by authors named "Yanling Teng"

15 Publications

  • Page 1 of 1

Prenatal case of Simpson-Golabi-Behmel syndrome with a de novo 370Kb-sized microdeletion of Xq26.2 compassing partial GPC3 gene and review.

Mol Genet Genomic Med 2021 Aug 22;9(8):e1750. Epub 2021 Jul 22.

Department of Medical Genetics, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan, China.

Background: Simpson-Golabi-Behmel syndrome type 1 (SGBS1) is a rare X-linked recessive disorder characterized by pre- and postnatal overgrowth and a broad spectrum of anomalies including craniofacial dysmorphism, heart defects, renal, and genital anomalies. Due to the ultrasound findings are not pathognomonic for this syndrome, most clinical diagnosis of SGBS1 are made postnatally.

Methods: A pregnant woman with abnormal prenatal sonographic findings was advised to perform molecular diagnosis. Single nucleotide polymorphism array (SNP array) was performed in the fetus, and the result was validated with multiplex ligation-dependent probe amplification (MLPA) and real-time quantitative PCR (qPCR).

Results: The prenatal sonographic presented with increased nuchal translucency at 13 gestational weeks, and later at 21 weeks with cleft lip and palate, heart defect, increased amniotic fluid index and over growth. A de novo 370Kb-deletion covering the 5'-UTR and exon 1 of GPC3 gene was detected in the fetus by SNP array, which was subsequently confirmed by MLPA and qPCR.

Conclusion: The de novo 370Kb hemizygous deletion of 5'-UTR and exon 1 of GPC3 results in the SGBS1 of this Chinese family. Combination of ultrasound and genetics tests helped us effectively to diagnose the prenatal cases of SGBS1. Our findings also enlarge the spectrum of mutations in GPC3 gene.
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http://dx.doi.org/10.1002/mgg3.1750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404223PMC
August 2021

A More Universal Approach to Comprehensive Analysis of Thalassemia Alleles (CATSA).

J Mol Diagn 2021 Sep 20;23(9):1195-1204. Epub 2021 Jul 20.

Department of Molecular Genetics, Hunan Jiahui Genetics Hospital, Changsha, China; Center for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, China. Electronic address:

The aim of the study was to assess the clinical utility of a third-generation sequencing (TGS) approach termed comprehensive analysis of thalassemia alleles (CATSA) for identifying both α and β thalassemia genetic carrier status. Prospective blood samples (n = 1759) with abnormal hemoglobin parameters were screened for pathogenic thalassemia variants by CATSA on the PacBio TGS platform. In 1159 individuals, a total of 1317 pathogenic thalassemia variants were identified and confirmed by independent PCR-based tests. Of the total thalassemia variants detected, the α-variant -- (35.4%) and β-variant c.126_129delCTTT (15%) were the most common. CATSA was also able to detect three types of rare HBA structural variants as well as five rare HBA2, three HBA1, and 10 HBB single-nucleotide variations/insertions and deletions. Compared with standard thalassemia variant PCR panel testing, CATSA identified all panel variants present, with no false-negative results. Carrier assignment was improved through identification of rare variants missed by the panel test. On the basis of allelic coverage, reliability, and accuracy, TGS with long-range PCR presents a comprehensive approach with the potential to provide a universal solution for thalassemia genetic carrier screening. It is proposed that CATSA has immediate clinical utility as an effective carrier screening approach for at-risk couples.
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http://dx.doi.org/10.1016/j.jmoldx.2021.06.008DOI Listing
September 2021

Urine albumin-to-creatinine ratio within the normal range and risk of hypertension in the general population: A meta-analysis.

J Clin Hypertens (Greenwich) 2021 07 5;23(7):1284-1290. Epub 2021 Jun 5.

Department of Heart Function Test, The First People's Hospital of Lianyungang, Lianyungang, China.

Inconsistent findings on the association between urine albumin-to-creatinine ratio (UACR) and risk of hypertension have been reported. This meta-analysis sought to evaluate the association between the elevated level of UACR within the normal range and incident hypertension in the general population. We comprehensively searched PubMed and Embase databases until July 31, 2020. All longitudinal observational studies that assessed the association of elevated baseline level of UACR within the normal range with incident hypertension in the general population were included. The predictive value was estimated by pooling risk ratio (RR) with 95% confidence intervals (CI) for the highest versus the lowest category of UACR level. Nine articles (10 studies) involving 27 771 individuals were identified and analyzed. When compared with the lowest category of UACR, individuals with the highest UACR had a 1.75-fold (RR 1.75; 95% CI 1.47-2.09; p < .001) higher risk of hypertension in a random effect model. Gender-specific analysis indicated that the impact of UACR on the development of hypertension seemed to be stronger in women (RR 2.47; 95% CI 1.10-5.55; p = .029) than in men (RR 1.88; 95% CI 1.35-2.61; p < .001). An increased UACR within the normal range is independently associated with a higher risk of hypertension in the general population. Baseline UACR can be served as a predictor of incident hypertension in the general population.
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http://dx.doi.org/10.1111/jch.14263DOI Listing
July 2021

Molecular diagnosis for 55 fetuses with skeletal dysplasias by whole-exome sequencing: A retrospective cohort study.

Clin Genet 2021 08 9;100(2):219-226. Epub 2021 Jun 9.

Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of life sciences, Central South University, Changsha, Hunan, China.

Skeletal dysplasias (SDs) are common birth defects, but they are difficult to diagnose accurately according to only the limited phenotypic information available from ultrasound during the pregnancy. To evaluate the application of whole-exome sequencing (WES) and expand the data in the prenatal molecular diagnosis of fetuses with SDs, we collected 55 fetuses with SDs based on ultrasonographic features. WES of the fetuses or parent-fetus trio were subjected to sequential tests and produced a diagnostic yield of 64% (35/55). 65% (11/17) of families with a history of adverse pregnancies were diagnosed, 16 genes were involved and 37 different pathogenic or likely pathogenic variants were identified, including 14 novel variants, which were first reported in this study. De novo variants were identified in 21 cases (60%, 21/35) among the fetuses with a genetic diagnosis. The pathogenicity of two novel splice-site variants was confirmed by constructing minigene in vitro. Our results revealed that WES can provide new evidence for the relationship between the genotype and phenotype of fetuses with SDs, as well as broaden the mutation spectrum of detected genes, which is significant for prenatal diagnosis and genetic counseling.
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http://dx.doi.org/10.1111/cge.13976DOI Listing
August 2021

Loss of PIGK function causes severe infantile encephalopathy and extensive neuronal apoptosis.

Hum Genet 2021 May 4;140(5):791-803. Epub 2021 Jan 4.

Center for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, 110 Xiangya Road, Changsha, 410078, Hunan, China.

PIGK gene, encoding a key component of glycosylphosphatidylinositol (GPI) transamidase, was recently reported to be associated with inherited GPI deficiency disorders (IGDs). However, little is known about the specific downstream effects of PIGK on neurodevelopment due to the rarity of the disease and the lack of in vivo study. Here, we described 2 patients in a Chinese family presented with profound global developmental delay, severe hypotonia, seizures, and postnatal progressive global brain atrophy including hemisphere, cerebellar and corpus callosum atrophy. Two novel compound heterozygous variants in PIGK were identified via genetic analysis, which was proved to cause significant decrease of PIGK protein and reduced cell surface presence of GPI-APs in the patients. To explore the role of Pigk on embryonic and neuronal development, we constructed Pigk knock-down zebrafish and knock-in mouse models. Zebrafish injected with a small dose of morpholino oligonucleotides displayed severe developmental defects including small eyes, deformed head, curly spinal cord, and unconsumed yolk sac. Primary motor neuronal dysplasia and extensive neural cell apoptosis were further observed. Meanwhile, the mouse models, carrying the two variants respectively homologous with the patients, both resulted in complete embryonic lethality of the homozygotes, which suggested the intolerable effect caused by amino acid substitution of Asp204 as well as the truncated mutation. Our findings provide the in vivo evidence for the essential role of PIGK during the embryonic and neuronal development. Based on these data, we propose a basis for further study of pathological and molecular mechanisms of PIGK-related neurodevelopmental defects.
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http://dx.doi.org/10.1007/s00439-020-02243-2DOI Listing
May 2021

Biochemical and genetic characteristics of 40 neonates with carnitine deficiency.

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2020 Oct;45(10):1164-1171

Center for Medical Genetics, School of Life Sciences, Central South University, Changsha 410078.

Objectives: Primary carnitine deficiency (PCD) is a rare fatty acid metabolism disorder that can cause neonatal death. This study aims to analyze carnitine levels and detect SLC22A5 gene in newborns with carnitine deficiency, to provide a basis for early diagnosis of PCD, and to explore the relationship between carnitine in blood and SLC22A5 genotype.

Methods: A total of 40 neonates with low free carnitine (C0<10 μmol/L) in blood were the subjects of the study. SLC22A5 gene was detected by Sanger sequencing to analyze the value of carnitine, the results of gene test and their relationship.

Results: A total of 15 variants of SLC22A5 gene were detected, including 11 pathogenic or likely pathogenic variants and 4 variants of uncertain significance. There were 5 new mutations: c.288delG (p.G96fsX33), c.744_745insTCG (p.M258_L259insS), c.752A>G (p.Y251C), c.495 C>A (p.R165E), and c.1298T>C (p.M433T). We found 14 PCD patients including 2 homozygous mutations and 12 heterozygous mutations, 14 with 1 mutation, and 12 with no mutation among 40 children. The C0 concentration of children with SLC22A5 gene homozygous or complex heterozygous mutations was (4.95±1.62) μmol/L in the initial screening, and (3.90±1.33) μmol/L in the second screening. The C0 concentration of children with no mutation was (7.04±2.05) μmol/L in the initial screening, and (8.02±2.87) μmol/L in the second screening. There were significant differences between children with homozygous or compound heterozygous mutations and with no mutation in C0 concentration of the initial and the second screening (both <0.05), as well as between children with truncated mutation and with untruncated mutation in C0 concentration of the initial screening (=0.022).

Conclusions: There are 5 new mutations which enriched the mutation spectrum of SLC22A5 gene. C0<5 μmol/L is highly correlated with SLC22A5 gene homozygous or compound heterozygous mutations. Children with truncated mutation may have lower C0 concentration than that with untruncated mutation in the initial screening.
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http://dx.doi.org/10.11817/j.issn.1672-7347.2020.190241DOI Listing
October 2020

Detection of Spinal Muscular Atrophy Using a Duplexed Real-Time PCR Approach With Locked Nucleic Acid-Modified Primers.

Ann Lab Med 2021 01 25;41(1):101-107. Epub 2020 Aug 25.

Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.

Background: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder mainly caused by homozygous deletions that include exon 7 of the survival motor neuron 1 (SMN1) gene. A nearby paralog gene, SMN2, obstructs the specific detection of SMN1. We optimized a duplexed real-time PCR approach using locked nucleic acid (LNA)-modified primers to specifically detect SMN1.

Methods: An LNA-modified primer pair with 3' ends targeting SMN1 specific sites c.835-44g and c.840C was designed, and its specificity was examined by real-time PCR and Sanger Sequencing. A duplexed real-time PCR approach for amplifying SMN1 and control gene albumin (ALB) was developed. A randomized double-blind trial with 97 fresh peripheral blood samples and 25 dried blood spots (DBS) was conducted to evaluate the clinical efficacy of the duplexed approach. This new approach was then used to screen 753 newborn DBS.

Results: The LNA-modified primers exhibited enhanced specificity and 6.8% increased efficiency for SMN1 amplification, compared with conventional primers. After stabilizing the SMN1 test by optimizing the duplexed real-time PCR approach, a clinical trial validated that the sensitivity and specificity of our new approach for detecting SMA patients and carriers was 100%. Using this new approach, 15 of the screened 753 newborns were identified as carriers via DBS, while the rest were identified as normal individuals. These data reveal a carrier rate of 1.99% in Hunan province, South Central China.

Conclusions: We have developed a novel, specific SMN1 detection approach utilizing real-time PCR with LNA-modified primers, which could be applied to both prenatal carrier and newborn screening.
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http://dx.doi.org/10.3343/alm.2021.41.1.101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7443528PMC
January 2021

Six novel Mutation analysis of the androgen receptor gene in 17 Chinese patients with androgen insensitivity syndrome.

Clin Chim Acta 2020 Jul 27;506:180-186. Epub 2020 Mar 27.

Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan 410078, China; Hunan Jiahui Genetics Hospital, Changsha, Hunan 410078, China. Electronic address:

Background: Androgen insensitivity syndrome (AIS) is the most common type of 46, XY disorders of sex development (DSD), with a wide range of clinical heterogeneity, from male infertility, hypospadias to completely normal female external genitalia. Mutation of the androgen receptor (AR) gene on the X chromosome (Xq11.2q12) is the main cause of AIS.

Methods: By phenotype evaluation, hormone test, ultrasound scan and G-banding karyotype, 17 unrelated Chinese patients were clinical diagnosed with AIS. Sanger sequencing of the AR was performed in these 17 patients. Functional studies were carried out for the novel mutations.

Results: We identified 16 mutations in all patients, including six novel mutations (Q59*, F171Sfs*4, E204*, G209E, I870T, *921R). It is the first time that a stop codon mutation (*921R) in AR has been identified. Expression and nuclear localization analysis showed the *921R mutation caused an elongated abnormal polypeptide chain of the AR protein, and the abnormal protein could not be transported to the nucleus to stimulate the expression of downstream genes after androgenic treatment. Expression analysis showed the protein level of G209E mutation was obviously decreased.

Conclusion: Our study expands the spectrum of AR mutations and could provide evidence for the genetic and reproductive counseling of families with AIS. All of these findings broadened the mutation spectrum of AR, which were significantly valuable for patient gender assignment, genetic counseling and the clinical and psychological management.
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http://dx.doi.org/10.1016/j.cca.2020.03.036DOI Listing
July 2020

A novel GJB1 mutation associated with X-linked Charcot-Marie-Tooth disease in a large Chinese family pedigree.

Mol Genet Genomic Med 2020 03 14;8(3):e1127. Epub 2020 Jan 14.

Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, China.

Background: Charcot-Marie-Tooth (CMT) disease is a group of hereditary neuropathies with high phenotypic and genetic heterogeneity. In this study, we report a large family with X-linked CMT (CMTX) caused by a novel GJB1 mutation.

Methods: A family with the clinical diagnosis of CMTX was investigated. For mutation analysis, the coding region of GJB1 was sequenced using DNA from 15 family members. The identified GJB1 mutation was investigated by DHPLC in 120 normal controls. Mutation reanalysis was performed based on whole-exome sequencing (WES). Cell transfection studies were performed to characterize the function of the novel mutation.

Results: A missense mutation (c.605T>A) in GJB1 was detected in five patients and eight female carriers but not in two unaffected members of the family. The mutation was not found in 120 healthy controls and has not been previously reported. WES excluded other pathogenic mutations in the family. The pathogenicity of the mutation was confirmed by disrupting the membrane localization of the encoded proteins.

Conclusion: Our findings demonstrate that a novel mutation (c.605T>A) in GJB1 is associated with CMTX and adds to the repertoire of GJB1 mutations related to CMTX.
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http://dx.doi.org/10.1002/mgg3.1127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057093PMC
March 2020

[Prenatal diagnosis for 30 women carrying a FMR1 mutation].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2019 Sep;36(9):866-869

Center for Medical Genetics, School of Life Science, Central South University, Changsha, Hunan 410078, China.

Objective: To determine the CGG repeat number and methylation status of FMR1 gene for fetuses whose mothers have carried a FMR1 mutation.

Methods: For 30 pregnant women, the fetal CGG repeat number was determined with a GC-rich PCR system by using chorionic villus, amniotic fluid or umbilical blood samples. The methylation status of the FMR1 gene was confirmed with Southern blotting.

Results: In total 30 prenatal diagnoses were performed for 29 carriers of FMR1 gene mutations and 1 with FMR1 gene deletion mosaicism. Three fetuses were found to carry premutations, 9 were with full mutations and 1 with mosaicism of premutation and full mutations. Eighteen fetuses were normal.

Conclusion: Considering the genetic complexity of Fragile X syndrome (FXS), single method may not suffice accurate determination of their genetic status. The pitfalls and technical limitations of protocols requires adoption of personalized strategy for its prenatal diagnosis.
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http://dx.doi.org/10.3760/cma.j.issn.1003-9406.2019.09.003DOI Listing
September 2019

Identification of pathogenic mutations in 6 Chinese families with multiple exostoses by whole-exome sequencing and multiplex ligation-dependent probe amplification: Case series.

Medicine (Baltimore) 2019 May;98(20):e15692

Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University.

Rationale: Hereditary multiple exostoses (HMEs) is an autosomal dominant skeletal disorder.

Patient Concerns: Six probands of the 6 unrelated Han Chinese families were identified as having HME. These patients had exostoses at multiple sites and significantly affected joints malformation and movement.

Diagnoses: Hereditary multiple exostoses.

Interventions: To detect the genetic mechanism of HME in 6 unrelated Chinese families, whole-exome sequencing (WES) and multiplex ligation-dependent probe amplification (MLPA) were used after genomic DNA was isolated from peripheral blood leucocytes. Point mutations identified by these methods were verified by Sanger sequencing after PCR amplification.

Outcomes: Six mutations in the EXT1 and EXT2 genes were identified, including a heterozygous deletion mutation from exon 2 to exon 8 (Family 1), a c.448C>T, p.(Gln150X) heterozygous nonsense mutation (Family 4), a c.1057-2A>T heterozygous splicing substitution (Family 5), and a c.1468dupC, p.(Leu490fs519X) (Family 6) heterozygous duplication mutation in the EXT1 gene in addition to a heterozygous deletion mutation from exon 2 to exon 3 (Family 2) and a c.1197C>G, p.(Tyr399X) heterozygous nonsense mutation (Family 3) in the EXT2 gene.

Lessons: Overall, we identified 5 novel mutations and 1 recurrent mutation in the EXT1 and EXT2 genes in 6 Chinese families with HME. Our findings expand the mutational spectrum of the EXT1 and EXT2 genes and are useful for genetic counseling and prenatal diagnosis.
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http://dx.doi.org/10.1097/MD.0000000000015692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6531242PMC
May 2019

Diagnosis of Joubert Syndrome 10 in a Fetus with Suspected Dandy-Walker Variant by WES: A Novel Splicing Mutation in .

Biomed Res Int 2018 15;2018:4032543. Epub 2018 Nov 15.

Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.

Joubert syndrome (JBTS) is a clinically and genetically heterogeneous group of ciliary diseases. To date, 34 subtypes of JBTS have been classified due to different causative genes or extra clinical features. Most of them are autosomal recessive, while only the subtype 10 (JBTS10) is a quite rare X-linked recessive disorder caused by mutations with few reports. In this study, by using whole exome sequencing (WES), a novel splicing mutation (c.2488+2T>C) was identified in a male fetus with suspected Dandy-Walker variant (DWV) and syndactyly, for whom abnormal karyotype and pathogenic CNV have been excluded. This mutation was inherited from the mother who has experienced two similar pregnancies before. An abnormal skipping of exon 18 in mRNA was confirmed by RT-PCR and sequencing. Result from quantitative RT-PCR also showed that total mRNA in the index fetus was significantly lower than the control. After a combined analysis of genetic testing results and genotype-phenotype correlations, the novel mutation c.2488+2T>C in was considered to be the genetic cause for the affected fetus. Thus the diagnosis should be JBTS10 rather than the primary clinical diagnosis of DWV. We report the first prenatal case of JBTS10 in Chinese population, which not only helps the family to predict recurrence risks for future pregnancies but also provides more information for understanding such a rare disease. The results also present evidence that WES is an effective method in prenatal diagnosis for those fetuses with Joubert syndrome.
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http://dx.doi.org/10.1155/2018/4032543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6276521PMC
April 2019

The survival motor neuron gene smn-1 interacts with the U2AF large subunit gene uaf-1 to regulate Caenorhabditis elegans lifespan and motor functions.

RNA Biol 2014 ;11(9):1148-60

a State Key Laboratory of Medical Genetics; School of Life Sciences ; Central South University ; Changsha , Hunan , China.

Spinal muscular atrophy (SMA), the most frequent human congenital motor neuron degenerative disease, is caused by loss-of-function mutations in the highly conserved survival motor neuron gene SMN1. Mutations in SMN could affect several molecular processes, among which aberrant pre-mRNA splicing caused by defective snRNP biogenesis is hypothesized as a major cause of SMA. To date little is known about the interactions of SMN with other splicing factor genes and how SMN affects splicing in vivo. The nematode Caenorhabditis elegans carries a single ortholog of SMN, smn-1, and has been used as a model for studying the molecular functions of SMN. We analyzed RNA splicing of reporter genes in an smn-1 deletion mutant and found that smn-1 is required for efficient splicing at weak 3' splice sites. Genetic studies indicate that the defective lifespan and motor functions of the smn-1 deletion mutants could be significantly improved by mutations of the splicing factor U2AF large subunit gene uaf-1. In smn-1 mutants we detected a reduced expression of U1 and U5 snRNAs and an increased expression of U2, U4 and U6 snRNAs. Our study verifies an essential role of smn-1 for RNA splicing in vivo, identifies the uaf-1 gene as a potential genetic modifier of smn-1 mutants, and suggests that SMN-1 has multifaceted effects on the expression of spliceosomal snRNAs.
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http://dx.doi.org/10.4161/rna.36100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4615316PMC
September 2015

The Caenorhabditis elegans gene mfap-1 encodes a nuclear protein that affects alternative splicing.

PLoS Genet 2012 19;8(7):e1002827. Epub 2012 Jul 19.

State Key Laboratory of Medical Genetics, School of Biological Sciences and Technology, Central South University, Changsha, China.

RNA splicing is a major regulatory mechanism for controlling eukaryotic gene expression. By generating various splice isoforms from a single pre-mRNA, alternative splicing plays a key role in promoting the evolving complexity of metazoans. Numerous splicing factors have been identified. However, the in vivo functions of many splicing factors remain to be understood. In vivo studies are essential for understanding the molecular mechanisms of RNA splicing and the biology of numerous RNA splicing-related diseases. We previously isolated a Caenorhabditis elegans mutant defective in an essential gene from a genetic screen for suppressors of the rubberband Unc phenotype of unc-93(e1500) animals. This mutant contains missense mutations in two adjacent codons of the C. elegans microfibrillar-associated protein 1 gene mfap-1. mfap-1(n4564 n5214) suppresses the Unc phenotypes of different rubberband Unc mutants in a pattern similar to that of mutations in the splicing factor genes uaf-1 (the C. elegans U2AF large subunit gene) and sfa-1 (the C. elegans SF1/BBP gene). We used the endogenous gene tos-1 as a reporter for splicing and detected increased intron 1 retention and exon 3 skipping of tos-1 transcripts in mfap-1(n4564 n5214) animals. Using a yeast two-hybrid screen, we isolated splicing factors as potential MFAP-1 interactors. Our studies indicate that C. elegans mfap-1 encodes a splicing factor that can affect alternative splicing.
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http://dx.doi.org/10.1371/journal.pgen.1002827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3400559PMC
January 2013

In vivo effects on intron retention and exon skipping by the U2AF large subunit and SF1/BBP in the nematode Caenorhabditis elegans.

RNA 2011 Dec 27;17(12):2201-11. Epub 2011 Oct 27.

State Key Laboratory of Medical Genetics, School of Biological Sciences and Technology, Central South University, Changsha, Hunan, China.

The in vivo analysis of the roles of splicing factors in regulating alternative splicing in animals remains a challenge. Using a microarray-based screen, we identified a Caenorhabditis elegans gene, tos-1, that exhibited three of the four major types of alternative splicing: intron retention, exon skipping, and, in the presence of U2AF large subunit mutations, the use of alternative 3' splice sites. Mutations in the splicing factors U2AF large subunit and SF1/BBP altered the splicing of tos-1. 3' splice sites of the retained intron or before the skipped exon regulate the splicing pattern of tos-1. Our study provides in vivo evidence that intron retention and exon skipping can be regulated largely by the identities of 3' splice sites.
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http://dx.doi.org/10.1261/rna.027458.111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3222132PMC
December 2011
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