University of Exeter Medical School

Dr Tom Laver

Dr Tom Laver

Lecturer in Diabetes

 twl207@exeter.ac.uk

 8232

 +44 (0) 1392 728232

 RILD Building Level 3

 

University of Exeter Medical School, RILD Building, RD&E Hospital Wonford, Barrack Road, Exeter, EX2 5DW, UK

Overview

Tom Laver is a bioinformatician and geneticist specialising in analysis of DNA sequencing data. He received a BSc in Biology from the University of Bath in 2010. He then completed a bioinformatics PhD at the University of Exeter on computational metagenomics. Tom joined the monogenic diabetes group at the University of Exeter Medical School in 2015. He became a Lecturer in Diabetes in 2020. His work is currently focused on using analysis of DNA sequencing data to discover novel genetic causes of hyperinsulinism and monogenic diabetes.

Qualifications

  • 2021 Postgraduate Certificate in Academic Practice & Fellowship of the Higher Education Academy (University of Exeter)
  • 2015 PhD in computational bacterial metagenomics (Biosciences, Univeristy of Exeter)
  • 2010 BSc. Biology (University of Bath)

Research group links

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Research

Research interests

Tom Laver works on monogenic disorders of insulin secretion with publications on hyperinsulinism and monogenic diabetes as well as on methodological aspects of studying the genetics of Mendelian diseases. He is bioinformatician and geneticist who specialises in analysis of DNA sequencing data including short read sequencing from Illumina and BGI, and long read sequencing from Pacific Biosciences and Oxford Nanopore. He is interested in the development and evaluation of bioinformatics tools. He has done extensive work on re-evaluating pathogenicity and penetrance of Mendelian disease genes. His work is currently focused on using analysis of DNA sequencing data to discover novel genetic causes of hyperinsulinism and monogenic diabetes.

Research projects

Using next-generation sequencing analysis to identify novel genetic aetiologies for hyperinsulinism and monogenic diabetes

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Publications

Journal articles

Wakeling M, Owens NDL, Hopkinson JR, Johnson MB, Houghton JAL, Dastamani A, Flaxman CS, Wyatt RC, Hewat TI, Hopkins JJ, et al (In Press). A novel disease mechanism leading to the expression of a disallowed gene in the pancreatic beta-cell identified by non-coding, regulatory mutations controlling HK1. Nature Genetics Abstract.
Laver TW, Wakeling M, Hua JHY, Houghton J, Hussain K, Ellard S, Flanagan S (In Press). Comprehensive screening shows that mutations in the known syndromic genes are rare in infants presenting with hyperinsulinaemic hypoglycaemia. Clinical Endocrinology
Hopkins J, Childs A, Houghton J, Hewat T, Atapattu N, Johnson M, Patel K, Laver T, Flanagan S (In Press). Hyperinsulinaemic hypoglycaemia diagnosed in childhood can be monogenic. The Journal of Clinical Endocrinology & Metabolism Abstract.
Hewat TI, Laver T, Houghton J, Mannisto J, Alvi S, Brearey S, Cody D, Dastamani A, de los Santos la Torre M, Murphy N, et al (In Press). Increased referrals for congenital hyperinsulinism genetic testing in children with trisomy 21 reflects the high burden of non-genetic risk factors in this group. Pediatric Diabetes
Caswell R, Snowsill T, Houghton J, Chakera A, Shepherd M, Laver T, Knight BA, Hattersley AT, Ellard S (In Press). Non-invasive fetal genotyping by droplet digital PCR to identify maternally-inherited monogenic diabetes variants. Clinical Chemistry
Houghton J, Laver T, Flanagan S (In Press). Unravelling the genetic causes of mosaic islet morphology in congenital hyperinsulinism. Journal of Pathology: Clinical Research
Laver TW, Wakeling MN, Caswell RC, Bunce B, Yau D, Männistö JME, Houghton JAL, Hopkins JJ, Weedon MN, Saraff V, et al (2024). Chromosome 20p11.2 deletions cause congenital hyperinsulinism via the loss of FOXA2 or its regulatory elements. Eur J Hum Genet Abstract.  Author URL.
Hopkins JJ, Wakeling MN, Johnson MB, Flanagan SE, Laver TW (2023). REVEL is Better at Predicting Pathogenicity of Loss-of-Function than Gain-of-Function Variants. Human Mutation, 2023, 1-6. Abstract.
Russ-Silsby J, Patel KA, Laver TW, Hawkes G, Johnson MB, Wakeling MN, Patil PP, Hattersley AT, Flanagan SE, Weedon MN, et al (2023). The Role of ONECUT1 Variants in Monogenic and Type 2 Diabetes Mellitus. Diabetes, 72(11), 1729-1734. Abstract.  Author URL.
Laver TW, Wakeling MN, Knox O, Colclough K, Wright CF, Ellard S, Hattersley AT, Weedon MN, Patel KA (2022). Evaluation of Evidence for Pathogenicity Demonstrates That BLK, KLF11, and PAX4 Should Not be Included in Diagnostic Testing for MODY. Diabetes, 71(5), 1128-1136. Abstract.  Author URL.
Patel KA, Burman S, Laver TW, Hattersley AT, Frayling TM, Weedon MN (2022). PLIN1 Haploinsufficiency Causes a Favorable Metabolic Profile. J Clin Endocrinol Metab, 107(6), e2318-e2323. Abstract.  Author URL.
Mirshahi UL, Colclough K, Wright CF, Wood AR, Beaumont RN, Tyrrell J, Laver TW, Stahl R, Golden A, Goehringer JM, et al (2022). Reduced penetrance of MODY-associated HNF1A/HNF4A variants but not GCK variants in clinically unselected cohorts. Am J Hum Genet, 109(11), 2018-2028. Abstract.  Author URL.
Laver TW, De Franco E, Johnson MB, Patel KA, Ellard S, Weedon MN, Flanagan SE, Wakeling MN (2022). SavvyCNV: Genome-wide CNV calling from off-target reads. PLOS Computational Biology, 18(3), e1009940-e1009940. Abstract.
Hewat TI, Yau D, Jerome JCS, Laver TW, Houghton JAL, Shields BM, Flanagan SE, Patel KA (2021). Birth weight and diazoxide unresponsiveness strongly predict the likelihood of congenital hyperinsulinism due to a mutation in ABCC8 or KCNJ11. European Journal of Endocrinology, 185(6), 813-818. Abstract.
Wakeling MN, Laver TW, Colclough K, Parish A, Ellard S, Baple EL (2020). Misannotation of multiple-nucleotide variants risks misdiagnosis. Wellcome Open Research, 4, 145-145. Abstract.
Banerjee I, Senniappan S, Laver TW, Caswell R, Zenker M, Mohnike K, Cheetham T, Wakeling MN, Ismail D, Lennerz B, et al (2020). Refinement of the critical genomic region for congenital hyperinsulinism in the Chromosome 9p deletion syndrome. Wellcome Open Research, 4, 149-149. Abstract.
Banerjee I, Senniappan S, Laver TW, Caswell R, Zenker M, Mohnike K, Cheetham T, Wakeling MN, Ismail D, Lennerz B, et al (2020). Refinement of the critical genomic region for congenital hyperinsulinism in the Chromosome 9p deletion syndrome. Wellcome open research, 4 Abstract.
De Franco E, Saint‐Martin C, Brusgaard K, Knight Johnson AE, Aguilar‐Bryan L, Bowman P, Arnoux J, Larsen AR, Sanyoura M, Greeley SAW, et al (2020). Update of variants identified in the pancreatic β‐cell K. <sub>ATP</sub>. channel genes. <i>KCNJ11</i>. and. <i>ABCC8</i>. in individuals with congenital hyperinsulinism and diabetes. Human Mutation, 41(5), 884-905.
Yau D, Laver TW, Dastamani A, Senniappan S, Houghton JAL, Shaikh G, Cheetham T, Mushtaq T, Kapoor RR, Randell T, et al (2020). Using referral rates for genetic testing to determine the incidence of a rare disease: the minimal incidence of congenital hyperinsulinism in the UK is 1 in 28,389. PLOS ONE, 15(2), e0228417-e0228417.
De Franco E, Lytrivi M, Ibrahim H, Montaser H, Wakeling M, Fantuzzi F, Patel K, Demarez C, Cai Y, Igoillo-Esteve M, et al (2020). YIPF5 mutations cause neonatal diabetes and microcephaly through endoplasmic reticulum stress. Journal of Clinical Investigation, 130
Wright CF, West B, Tuke M, Jones SE, Patel K, Laver TW, Beaumont RN, Tyrrell J, Wood AR, Frayling TM, et al (2019). Assessing the Pathogenicity, Penetrance, and Expressivity of Putative Disease-Causing Variants in a Population Setting. American Journal of Human Genetics, 104(2), 275-286. Abstract.
Wakeling MN, Laver TW, Wright CF, De Franco E, Stals KL, Patch A-M, Hattersley AT, Flanagan SE, Ellard S, DDD Study, et al (2019). Homozygosity mapping provides supporting evidence of pathogenicity in recessive Mendelian disease. Genet Med, 21(4), 982-986. Abstract.  Author URL.
Wakeling MN, Laver TW, Colclough K, Parish A, Ellard S, Baple EL (2019). Misannotation of multiple-nucleotide variants risks misdiagnosis. Wellcome Open Research, 4, 145-145. Abstract.
Banerjee I, Senniappan S, Laver TW, Caswell R, Zenker M, Mohnike K, Cheetham T, Wakeling MN, Ismail D, Lennerz B, et al (2019). Refinement of the critical genomic region for hypoglycaemia in the Chromosome 9p deletion syndrome. Wellcome Open Research, 4, 149-149. Abstract.
Laver TW, De Franco E, Johnson MB, Patel K, Ellard S, Weedon MN, Flanagan SE, Wakeling MN (2019). SavvyCNV: genome-wide CNV calling from off-target reads. Abstract.
Laver TW, Wakeling MN, Hong Yeow Hua J, Houghton JAL, Hussain K, Ellard S, Flanagan SE (2018). Comprehensive screening shows that mutations in the known syndromic genes are rare in individuals presenting with hyperinsulinaemic hypoglycaemia. Abstract.
Laver TW, Patel KA, Colclough K, Curran J, Dale J, Davis N, Savage DB, Flanagan SE, Ellard S, Hattersley AT, et al (2018). PLIN1 Haploinsufficiency is Not Associated with Lipodystrophy. J Clin Endocrinol Metab, 103(9), 3225-3230. Abstract.  Author URL.
Laver T, Wakeling M, Knox O, De-Franco E, Flanagan S, Colclough K, Ellard S, Hattersley A, Weedon M, Patel K, et al (2018). Redefining the pathogenicity of Maturity Onset Diabetes of the Young (MODY) genes: BLK, PAX4 and KLF11 do not cause MODY. DIABETIC MEDICINE, 35, 10-10.  Author URL.
Locke JM, Saint-Martin C, Laver TW, Patel KA, Wood AR, Sharp SA, Ellard S, Bellanné-Chantelot C, Hattersley AT, Harries LW, et al (2018). The Common HNF1A Variant I27L is a Modifier of Age at Diabetes Diagnosis in Individuals with HNF1A-MODY. Diabetes, 67(9), 1903-1907. Abstract.  Author URL.
Flanagan SE, Vairo F, Johnson MB, Caswell R, Laver TW, Lango Allen H, Hussain K, Ellard S (2017). A CACNA1D mutation in a patient with persistent hyperinsulinaemic hypoglycaemia, heart defects, and severe hypotonia. Pediatr Diabetes, 18(4), 320-323. Abstract.  Author URL.
Laver TW, Weedon MN, Caswell R, Hussain K, Ellard S, Flanagan SE (2017). Analysis of large-scale sequencing cohorts does not support the role of variants in UCP2 as a cause of hyperinsulinaemic hypoglycaemia. Hum Mutat, 38(10), 1442-1444.  Author URL.
Patel KA, Kettunen J, Laakso M, Stančáková A, Laver TW, Colclough K, Johnson MB, Abramowicz M, Groop L, Miettinen PJ, et al (2017). Heterozygous <i>RFX6</i> protein truncating variants are associated with Maturity-Onset Diabetes of the Young (MODY) with reduced penetrance. Abstract.
Patel KA, Kettunen J, Laakso M, Stančáková A, Laver TW, Colclough K, Johnson MB, Abramowicz M, Groop L, Miettinen PJ, et al (2017). Heterozygous RFX6 protein truncating variants are associated with MODY with reduced penetrance. Nat Commun, 8(1). Abstract.  Author URL.
Laver TW, Caswell RC, Moore KA, Poschmann J, Johnson MB, Owens MM, Ellard S, Paszkiewicz KH, Weedon MN (2016). Pitfalls of haplotype phasing from amplicon-based long-read sequencing. Sci Rep, 6 Abstract.  Author URL.
Laver TW, Colclough K, Shepherd M, Patel K, Houghton JAL, Dusatkova P, Pruhova S, Morris AD, Palmer CN, McCarthy MI, et al (2016). The Common p.R114W HNF4A Mutation Causes a Distinct Clinical Subtype of Monogenic Diabetes. Diabetes, 65(10), 3212-3217. Abstract.  Author URL.
Laver T, Harrison J, O'Neill PA, Moore K, Farbos A, Paszkiewicz K, Studholme DJ (2015). Assessing the performance of the Oxford Nanopore Technologies MinION. Biomolecular Detection and Quantification, 3, 1-8. Abstract.
O'Sullivan DM, Laver T, Temisak S, Redshaw N, Harris KA, Foy CA, Studholme DJ, Huggett JF (2014). Assessing the accuracy of quantitative molecular microbial profiling. Int J Mol Sci, 15(11), 21476-21491. Abstract.  Author URL.
Huggett JF, Laver T, Tamisak S, Nixon G, O'Sullivan DM, Elaswarapu R, Studholme DJ, Foy CA (2013). Considerations for the development and application of control materials to improve metagenomic microbial community profiling. Accreditation and Quality Assurance, 18(2), 77-83. Abstract.
Huggett JF, Studholme DJ, Laver T, Foy CA (2013). Progress in metagenomics requires a balanced appraisal of the available technologies. European Journal of Clinical Microbiology and Infectious Diseases, 32(8), 1097-1098.
Huggett JF, Studholme DJ, Laver T, Foy CA (2013). Progress in metagenomics requires a balanced appraisal of the available technologies. Eur J Clin Microbiol Infect Dis, 32(8), 1097-1098.  Author URL.

Conferences

Colclough K, Sharpe L, Laver T, Hattersley A, Weedon M, Patel K (2023). Rare missense and protein truncating variants in NEUROD1 and PDX1, but not APPL1, cause MODY with reduced penetrance.  Author URL.
Patel K, Mirshahi U, Colclough K, Wright C, Wood A, Beaumont R, Laver T, Stahl R, Golden A, Goehringer J, et al (2022). Penetrance of MODY is substantially lower in clinically unselected cohort: important implications for opportunistic genomic testing.  Author URL.
Laver TW, Wakeling MN, Knox O, Colclough K, Wright C, Ellard S, Hattersley AT, Weedon MN, Patel KA (2022). Re-evaluation of gene pathogenicity for MODY.  Author URL.
Mirshahi UL, Colclough K, Wright C, Laver T, Stahl R, Golden A, Goehringer J, Hattersley AT, Carey DJ, Weedon M, et al (2022). The penetrance of age-dependent monogenic disease variants depends on ascertainment context.  Author URL.
Hopkins J, Childs A, Hewat T, Patel K, Houghton J, Johnson M, Laver T, Flanagan S (2021). Congenital hyperinsulinism diagnosed after 12 months can have a monogenic aetiology.  Author URL.
Wakeling MN, De Franco E, Laver TW, Flanagan SE, Johnson M, Patel K, Hattersley AT, Ellard S (2019). Homozygosity mapping from small targeted NGS panels using SavvyHomozygosity - getting more from less.  Author URL.
Laver TW, Wakeling MN, Caswell R, Bunce B, Houghton JAL, Patel KA, Hussain K, Ellard S, Flanagan S (2019). Large deletions are an underappreciated cause of hyperinsulinism.  Author URL.
West B, Wright CF, Tuke MA, Jones S, Patel K, Laver TW, Beaumont RN, Tyrrell J, Wood AR, Murray A, et al (2019). Using UK Biobank to assess the pathogenicity, penetrance and expressivity of monogenic disease variants.  Author URL.
Patel KA, Laakso M, Stancakova A, Laver T, Colclough K, Johnson M, Kettunen J, Tuomi T, Cnop M, Shepherd M, et al (2017). Heterozygous Protein-Truncating RFX6 Variants Cause MODY with Reduced Penetrance.  Author URL.
Patel KA, Laver T, Johnson M, Sanders T, Shepherd M, Ellard S, Flanagan S, Hattersley AT, Weedon MN (2016). RFX6 is a new MODY gene.  Author URL.

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Teaching

Tom Laver teaches on a variety of modules within the Medical School. These have included BSc Medical Sciences: Medical Genetics and Integrated Human Physiology modules, SSUs and PBL for the BMBS Medicine course, and Bioinformatics and Genomics of Common and Rare Inherited Disease modules on the MSc Genomic Medicine course. Tom supervises final year research projects for BSc Medical Sciences and MSc Genomic Medicine. He also offers summer research projects and PTYs. He is module lead for the Genomics of Common and Rare Inherited Diseases MSc module. 

Postgraduate Research opportunities: Tom is open to enquiries from students with their own funding interested in pursuing an MSc by Research or PhD in genetics, diabetes, hyperinsulinism or related  research. 

Modules

2023/24


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