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Contact Details

Phone
+64 3 479 5056
Email
louise.bicknell@otago.ac.nz

University Links

Position
Associate Professor
Department
Department of Biochemistry
Qualifications
BSc(Hons) PhD
Research summary
Genetics of rare disorders
Teaching
GENE411, GENE360, BIOC360, BIOC463
Memberships
  • Co-Deputy Director, Genetics Otago
  • Regional Representative, Human Genetics Society of Australasia
  • Co-Chair, Personal Awards Committee, Neurological Foundation of New Zealand

Research

Louise repatriated to Otago from the University of Edinburgh in 2015 with a Rutherford Discovery Fellowship, and was thereafter supported by an inaugural HRC Consolidator Grant. She joined the Department of Biochemistry as a Senior Lecturer in 2021. In 2020 Louise was awarded the Rowheath Trust Award and Carl Smith Medal from the University of Otago. Her group’s work is supported by grants from the Health Research Council of New Zealand, Cure Kids, Neurological Foundation of New Zealand (including support from the Broad Family Trust), University of Otago and the Marsden Fund.

Bicknell laboratory logo Rare disorder genetics

Our research centres around understanding how alterations in our DNA can influence or cause genetic conditions. We are people-focused, studying families from New Zealand and overseas where a child is affected by a rare genetic disorder. Using DNA sequencing and cell biology, we aim to identify the causes of these disorders. Our ultimate goal is to be able to provide information to the family to help them understand the causes of their child’s condition, help with expectations for the future, and provide better information as to the chance of having more children who are also affected.

We have several disorders we are particularly focused on.

Meier-Gorlin syndrome and DNA replication

Meier-Gorlin syndrome is a very rare genetic disorder, with approximately 80 patients known about from around the world, including only 2-3 from New Zealand. Children are both small, and often have a small head (microcephaly), small ears (microtia) and small or absent kneecaps. There are some facial features which can clinically aid in diagnosing Meier-Gorlin syndrome.

We have a long track-record in studying this syndrome, and have identified most of the genes involved (eg Bicknell et al., Nat Genet 2011a, 2011b; Knapp et al, J Med Genet 2020, Knapp et al Eur J Hum Genet 2021), including three genes through a 2015 Marsden-funded project. All genes are involved in the earliest stages of DNA replication, a complex process required in almost every cell, where new DNA is synthesised for partitioning into a daughter cell as the cells grow and divide. We continue to study patients with this condition to further identify other genes important in this syndrome, but also to understand why specific body parts, like ears and kneecaps, are so sensitive to the mutations. We are also interested in harnessing the power of these mutations as a growth restrictor, for their potential involvement in cancer.

genes associated with Meier-Gorlin syndrome play essential roles as part of bigger complexes in the initiation of DNA replication

Syndromic Microcephaly

Supported by the Neurological Foundation, we are studying children with New Zealand with a significantly reduced head size (microcephaly). We identify mutations in approximately 50% of the patients we study, in a mixture of established disease genes and novel candidate genes, which we investigate further using both cellular and animal models, and gather more patients through our international networks.

Developmental disorders in New Zealand children

We also study children with a variety of developmental disorders, often including intellectual disability and/or short stature. Using exome sequencing as a starting point, we aim to identify the pathogenic variants, and delve deeper in studying patients with an atypical feature or a novel genetic disorder.

Publications

Schoch, K., Ruegg, M. S. G., Fellows, B. J., Cao, J., Uhrig, S., Einsele-Scholz, S., … Hawarden, S. R. A., … Brown, C. M., … Bicknell, L. S. (2024). A second hotspot for pathogenic exon-skipping variants in CDC45. European Journal of Human Genetics. Advance online publication. doi: 10.1038/s41431-024-01583-1

Fellows, B. J., Tolezano, G. C., Pires, S. F., Ruegg, M. S. G., Knapp, K. M., Krepischi, A. C. V., & Bicknell, L. S. (2023). A novel KNL1 intronic splicing variant likely destabilizes the KMN complex, causing primary microcephaly [Case report]. American Journal of Medical Genetics Part A. Advance online publication. doi: 10.1002/ajmg.a.63468

Mulligan, M. R., & Bicknell, L. S. (2023). The molecular genetics of nELAVL in brain development and disease. European Journal of Human Genetics. Advance online publication. doi: 10.1038/s41431-023-01456-z

Nielsen Dandoroff, E., Ruegg, M. S. G., & Bicknell, L. S. (2023). The expanding genetic and clinical landscape associated with Meier-Gorlin syndrome. European Journal of Human Genetics. Advance online publication. doi: 10.1038/s41431-023-01359-z

Knapp, K., Naik, N., Ray, S., van Haaften, G., & Bicknell, L. S. (2023). Histones: Coming of age in Mendelian genetic disorders. Journal of Medical Genetics. Advance online publication. doi: 10.1136/jmg-2022-109085

Schoch, K., Ruegg, M. S. G., Fellows, B. J., Cao, J., Uhrig, S., Einsele-Scholz, S., … Hawarden, S. R. A., … Brown, C. M., … Bicknell, L. S. (2024). A second hotspot for pathogenic exon-skipping variants in CDC45. European Journal of Human Genetics. Advance online publication. doi: 10.1038/s41431-024-01583-1

Journal - Research Article

Tessadori, F., Duran, K., Knapp, K., Fellner, M., Deciphering Developmental Disorders Study, Smithson, S., … Robertson, S. P., … Mace, P. D., Bicknell, L. S., & van Haaften, G. (2022). Recurrent de novo missense variants across multiple histone H4 genes underlie a neurodevelopmental syndrome. American Journal of Human Genetics, 109, 750-758. doi: 10.1016/j.ajhg.2022.02.003

Journal - Research Article

Blakes, A. J. M., Gaul, E., Lam, W., Shannon, N., Knapp, K. M., Bicknell, L. S., Jackson, M. R., Wade, E. M., Robertson, S., … Douglas, A. G. L. (2021). Pathogenic variants causing ABL1 malformation syndrome cluster in a myristoyl-binding pocket and increase tyrosine kinase activity. European Journal of Human Genetics, 29, 593-603. doi: 10.1038/s41431-020-00766-w

Journal - Research Article

Knapp, K. M., Fellows, B., Aggarwal, S., Dalal, A., & Bicknell, L. S. (2021). A synonymous variant in a non-canonical exon of CDC45 disrupts splicing in two affected sibs with Meier-Gorlin syndrome with craniosynostosis. European Journal of Medical Genetics, 64(4), 104182. doi: 10.1016/j.ejmg.2021.104182

Journal - Research Article

Knapp, K. M., Jenkins, D. E., Sullivan, R., Harms, F. L., von Elsner, L., Ockeloen, C. W., … Bicknell, L. S. (2021). MCM complex members MCM3 and MCM7 are associated with a phenotypic spectrum from Meier-Gorlin syndrome to lipodystrophy and adrenal insufficiency. European Journal of Human Genetics, 29, 1110-1120. doi: 10.1038/s41431-021-00839-4

Journal - Research Article

Knapp, K. M., Luu, R., Baerenfaenger, M., Zijlstra, F., Wessels, H. J. C. T., Jenkins, D., … Bicknell, L. S. (2020). Biallelic variants in SLC35C1 as a cause of isolated short stature with intellectual disability. Journal of Human Genetics, 65, 743-750. doi: 10.1038/s10038-020-0764-4

Journal - Research Article

Knapp, K. M., Sullivan, R., Murray, J., Gimenez, G., Arn, P., D'Souza, P., … Bicknell, L. S. (2020). Linked-read genome sequencing identifies biallelic pathogenic variants in DONSON as a novel cause of Meier-Gorlin syndrome. Journal of Medical Genetics, 57, 195-202. doi: 10.1136/jmedgenet-2019-106396

Journal - Research Article

Tarnauskaitė, Ž., Bicknell, L. S., Marsh, J. A., Murray, J. E., Parry, D. A., Logan, C. V., … Reijns, M. A. M. (2019). Biallelic variants in DNA2 cause microcephalic primordial dwarfism. Human Mutation, 40, 1063-1070. doi: 10.1002/humu.23776

Journal - Research Article

Reynolds, J. J., Bicknell, L. S., Carroll, P., Higgs, M. R., Shaheen, R., Murray, J. E., … Stuart, G. S. (2017). Mutations in DONSON disrupt replication fork stability and cause microcephalic dwarfism. Nature Genetics, 49(4), 537-549. doi: 10.1038/ng.3790

Journal - Research Article

Fenwick, A. L., Kliszczak, M., Cooper, F., Murray, J., Sanchez-Pulido, L., Twigg, S. R. F., … Bicknell, L. S. (2016). Mutations in CDC45, encoding an essential component of the pre-initiation complex, cause Meier-Gorlin syndrome and craniosynostosis. American Journal of Human Genetics, 99(1), 125-138. doi: 10.1016/j.ajhg.2016.05.019

Journal - Research Article

Harley, M. E., Murina, O., Leitch, A., Higgs, M. R., Bicknell, L. S., Yigit, G., … Jackson, A. P. (2016). TRAIP promotes DNA damage response during genome replication and is mutated in primordial dwarfism. Nature Genetics, 48(1), 38-43. doi: 10.1038/ng.3451

Journal - Research Article

Martin, C.-A., Murray, J. E., Carroll, P., Leitch, A., Mackenzie, K. J., Halachev, M., … Bicknell, L. S., … Jackson, A. P. (2016). Mutations in genes encoding condensin complex proteins cause microcephaly through decatenation failure at mitosis. Genes & Development, 30, 2158-2172. doi: 10.1101/gad.286351.116

Journal - Research Article

Günther, C., Kind, B., Reijns, M. A. M., Berndt, N., Martinez-Bueno, M., Wolf, C., … Bicknell, L., … Lee-Kirsch, M. A. (2015). Defective removal of ribonucleotides from DNA promotes systemic autoimmunity. Journal of Clinical Investigation, 125(1), 413-424. doi: 10.1172/JCI78001

Journal - Research Article

Murray, J. E., van der Burg, M., IJspeert, H., Carroll, P., Wu, Q., Ochi, T., … Bicknell, L. S. (2015). Mutations in the NHEJ component XRCC4 cause primordial dwarfism. American Journal of Human Genetics, 96(3), 412-424. doi: 10.1016/j.ajhg.2015.01.013

Journal - Research Article

Waters, A. M., Asfahani, R., Carroll, P., Bicknell, L., Lescai, F., Bright, A., … Beales, P. L. (2015). The kinetochore protein, CENPF, is mutated in human ciliopathy and microcephaly phenotypes. Journal of Medical Genetics, 52(3), 147-156. doi: 10.1136/jmedgenet-2014-102691

Journal - Research Article

Martin, C.-A., Ahmad, I., Klingseisen, A., Hussain, M. S., Bicknell, L. S., Leitch, A., … Jackson, A. P. (2014). Mutations in PLK4, encoding a master regulator of centriole biogenesis, cause microcephaly, growth failure and retinopathy. Nature Genetics, 46(12), 1283-1292. doi: 10.1038/ng.3122

Journal - Research Article

Murray, J. E., Bicknell, L. S., Yigit, G., Duker, A. L., van Kogelenberg, M., Haghayegh, S., … Jackson, A. P. (2014). Extreme growth failure is a common presentation of ligase IV deficiency. Human Mutation, 35(1), 76-85. doi: 10.1002/humu.22461

Journal - Research Article

Lancaster, M. A., Renner, M., Martin, C.-A., Wenzel, D., Bicknell, L. S., Hurles, M. E., … Knoblich, J. A. (2013). Cerebral organoids model human brain development and microcephaly. Nature, 501(7467), 373-379. doi: 10.1038/nature12517

Journal - Research Article

Meynert, A. M., Bicknell, L. S., Hurles, M. E., Jackson, A. P., & Taylor, M. S. (2013). Quantifying single nucleotide variant detection sensitivity in exome sequencing. BMC Bioinformatics, 14, 195. doi: 10.1186/1471-2105-14-195

Journal - Research Article

Bober, M. B., Niiler, T., Duker, A. L., Murray, J. E., Ketterer, T., Harley, M. E., … Bicknell, L. S., … Jackson, A. P. (2012). Growth in individuals with Majewski osteodysplastic primordial dwarfism type II caused by pericentrin mutations. American Journal of Medical Genetics Part A, 158 A(11), 2719-2725. doi: 10.1002/ajmg.a.35447

Journal - Research Article

de Munnik, S. A., Bicknell, L. S., Aftimos, S., Al-Aama, J. Y., van Bever, Y., Bober, M. B., … Bongers, E. M. H. F. (2012). Meier-Gorlin syndrome genotype-phenotype studies: 35 individuals with pre-replication complex gene mutations and 10 without molecular diagnosis. European Journal of Human Genetics, 20(6), 598-606. doi: 10.1038/ejhg.2011.269

Journal - Research Article

de Munnik, S. A., Otten, B. J., Schoots, J., Bicknell, L. S., Aftimos, S., Al-Aama, J. Y., … Bongers, E. M. H. F. (2012). Meier-Gorlin syndrome: Growth and secondary sexual development of a microcephalic primordial dwarfism disorder. American Journal of Medical Genetics Part A, 158 A(11), 2733-2742. doi: 10.1002/ajmg.a.35681

Journal - Research Article

Bicknell, L. S., Bongers, E. M. H. F., Leitch, A., Brown, S., Schoots, J., Harley, M. E., … Jackson, A. P. (2011). Mutations in the pre-replication complex cause Meier-Gorlin syndrome. Nature Genetics, 43(4), 356-360. doi: 10.1038/ng.775

Journal - Research Article

Bicknell, L. S., Walker, S., Klingseisen, A., Stiff, T., Leitch, A., Kerzendorfer, C., … Jeggo, P. A. (2011). Mutations in ORC1, encoding the largest subunit of the origin recognition complex, cause microcephalic primordial dwarfism resembling Meier-Gorlin syndrome. Nature Genetics, 43(4), 350-356. doi: 10.1038/ng.776

Journal - Research Article

Huang-Doran, I., Bicknell, L. S., Finucane, F. M., Rocha, N., Porter, K. M., Tung, Y. C. L., … for the Majewski Osteodysplastic Primordial Dwarfism Study Group. (2011). Genetic defects in human pericentrin are associated with severe insulin resistance and diabetes. Diabetes, 60(3), 925-935. doi: 10.2337/db10-1334

Journal - Research Article

Kalay, E., Yigit, G., Aslan, Y., Brown, K. E., Pohl, E., Bicknell, L. S., … Wollnik, B. (2011). CEP152 is a genome maintenance protein disrupted in Seckel syndrome. Nature Genetics, 43(1), 23-26. doi: 10.1038/ng.725

Journal - Research Article

Leung, J. W., Leitch, A., Wood, J. L., Shaw-Smith, C., Metcalfe, K., Bicknell, L. S., … Chen, J. (2011). SET nuclear oncogene associates with microcephalin/MCPH1 and regulates chromosome condensation. Journal of Biological Chemistry, 286(24), 21393-21400. doi: 10.1074/jbc.M110.208793

Journal - Research Article

Rainger, J., van Beusekom, E., Ramsay, J. K., McKie, L., Al-Gazali, L., Pallotta, R., … Bicknell, L., … FitzPatrick, D. R. (2011). Loss of the BMP antagonist, SMOC-1, causes ophthalmo-acromelic (Waardenburg anophthalmia) syndrome in humans and mice. PLoS Genetics, 7(7), e1002114. doi: 10.1371/journal.pgen.1002114

Journal - Research Article

Bicknell, L. S., Pitt, J., Aftimos, S., Ramadas, R., Maw, M. A., & Robertson, S. P. (2008). A missense mutation in ALDH18A1, encoding Δ1-pyrroline-5-carboxylate synthase (P5CS), causes an autosomal recessive neurocutaneous syndrome. European Journal of Human Genetics, 16, 1176-1186. doi: 10.1038/ejhg.2008.91

Journal - Research Article

Bicknell, L. S., Farrington-Rock, C., Shafeghati, Y., Rump, P., Alanay, Y., Alembik, Y., … Robertson, S. P. (2007). A molecular and clinical study of Larsen syndrome caused by mutations in FLNB. Journal of Medical Genetics, 44, 89-98.

Journal - Research Article

Farrington-Rock, C., Firestein, M. H., Bicknell, L. S., Superti-Furga, A., Bacino, C. A., Cormier-Daire, V., … Robertson, S. P., … Krakow, D. (2006). Mutations in two regions of FLNB result in atelosteogenesis I and III. Human Mutation, 27(7), 705-710. doi: 10.1002/humu.20348

Journal - Research Article

Bicknell, L. S., Morgan, T., Bonafé, L., Wessels, M. W., Bialer, M. G., Willems, P. J., … Robertson, S. P. (2005). Mutations in FLNB cause boomerang dysplasia. Journal of Medical Genetics, 42(7), e43. doi: 10.1136/jmg.2004.029967

Journal - Research Article

Fellows, B. J., Tolezano, G. C., Pires, S. F., Ruegg, M. S. G., Knapp, K. M., Krepischi, A. C. V., & Bicknell, L. S. (2023). A novel KNL1 intronic splicing variant likely destabilizes the KMN complex, causing primary microcephaly [Case report]. American Journal of Medical Genetics Part A. Advance online publication. doi: 10.1002/ajmg.a.63468

Journal - Research Other

Knapp, K., Naik, N., Ray, S., van Haaften, G., & Bicknell, L. S. (2023). Histones: Coming of age in Mendelian genetic disorders. Journal of Medical Genetics. Advance online publication. doi: 10.1136/jmg-2022-109085

Journal - Research Other

Mulligan, M. R., & Bicknell, L. S. (2023). The molecular genetics of nELAVL in brain development and disease. European Journal of Human Genetics. Advance online publication. doi: 10.1038/s41431-023-01456-z

Journal - Research Other

Nielsen Dandoroff, E., Ruegg, M. S. G., & Bicknell, L. S. (2023). The expanding genetic and clinical landscape associated with Meier-Gorlin syndrome. European Journal of Human Genetics. Advance online publication. doi: 10.1038/s41431-023-01359-z

Journal - Research Other

Carter, S., Fellows, B. J., Gibson, K., & Bicknell, L. S. (2022). Extending the PAX1 spectrum: A dominantly inherited variant causes oculo-auriculo-vertebral syndrome. European Journal of Human Genetics, 30, 1178-1181. doi: 10.1038/s41431-022-01154-2

Journal - Research Other

Shelling, A. N., Bicknell, L. S., Bohlander, S. S., Cox, M. P., Filoche, S. K., Fraser, H. G., … Te Aika, B., Purcell, R. V., & Tiller, J. M. (2022). Genomic discrimination in New Zealand health and life insurance: AGenDA: Against Genomic Discrimination in Aotearoa. New Zealand Medical Journal, 135(1551), 7-12. Retrieved from https://www.nzma.org.nz/journal

Journal - Research Other

Knapp, K. M., Murray, J., Temple, I. K., & Bicknell, L. S. (2021). Successful pregnancies in an adult with Meier-Gorlin syndrome harboring biallelic CDT1 variants. American Journal of Medical Genetics Part A, 185A, 871-876. doi: 10.1002/ajmg.a.62016

Journal - Research Other

Knapp, K. M., Poke, G., Jenkins, D., Truter, W., & Bicknell, L. S. (2019). Expanding the phenotypic spectrum associated with DPF2: A new case report. American Journal of Medical Genetics Part A, 179A, 1637-1641. doi: 10.1002/ajmg.a.61262

Journal - Research Other

Llorens-Agost, M., Luessing, J., van Beneden, A., Eykelenboom, J., O'Reilly, D., Bicknell, L. S., … Lowndes, N. F. (2018). Analysis of novel missense ATR mutations reveals new splicing defects underlying Seckel Syndrome. Human Mutation, 39, 1847-1853. doi: 10.1002/humu.23648

Journal - Research Other

Logan, C. V., Murray, J. E., Parry, D. A., Robertson, A., Bellelli, R., Tarnauskaite, Z., … Bicknell, L. S., … Jackson, A. P. (2018). DNA polymerase epsilon deficiency causes IMAGe syndrome with variable immunodeficiency [Report]. American Journal of Human Genetics, 103(6), 1038-1044. doi: 10.1016/j.ajhg.2018.10.024

Journal - Research Other

Kroigard, A. B., Jackson, A. P., Bicknell, L. S., Baple, E., Brusgaard, K., Hansen, L. K., & Ousager, L. B. (2016). Two novel mutations in RNU4ATAC in two siblings with an atypical mild phenotype of microcephalic osteodysplastic primordial dwarfism type 1. Clinical Dysmorphology, 25(2), 68-72. doi: 10.1097/mcd.0000000000000110

Journal - Research Other

Pagnamenta, A. T., Murray, J. E., Yoon, G., Akha, E. S., Harrison, V., Bicknell, L. S., … Knight, S. J. L. (2012). A novel nonsense CDK5RAP2 mutation in a Somali child with primary microcephaly and sensorineural hearing loss [Clinical report]. American Journal of Medical Genetics Part A, 158 A(10), 2577-2582. doi: 10.1002/ajmg.a.35558

Journal - Research Other

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