Selected highlights
Quantifying constraint in the human mitochondrial genome.
Lake NJ‡, Ma K*, Liu W*, Battle SL, Laricchia KM, Tiao G, Puiu D, Ng KK, Cohen J, Compton AG, Cowie S, Christodoulou J, Thorburn DR, Zhao H, Arking DE, Sunyaev S, Lek M‡. ‡Corresponding author. *Co-second author. Nature, 2024. Highlighted in Nature Research Briefing - "Constraint reveals the mitochondrial genome sites most important for health and disease" |
Mitochondrial DNA variation across 56,434 individuals in gnomAD.
Laricchia KM*, Lake NJ*, Watts NA, Shand M, Haessly A, Gauthier L, Benjamin D, Banks E, Soto J, Garimella K, Emery J, Genome Aggregation Database Consortium, Rehm HL, MacArthur DG, Tiao G, Lek M, Mootha VK, Calvo SE. *Co-first author. Genome Research, 2022. |
MitoVisualize: a resource for analysis of variants in mitochondrial RNAs & DNA.
Lake NJ‡, Zhou L, Xu J, Lek M‡. ‡Corresponding author. Bioinformatics, 2022. |
Deleterious heteroplasmic mitochondrial mutations are associated with an increased risk of overall and cancer-specific mortality.
Hong YS*, Battle SL*, Shi W, Puiu D, Pillalamarri V, Xie J, Pankratz N, Lake NJ, Lek M, Rotter JI, Rich S, Kooperberg C, Reiner AP, Auer P, Heard-Costa N, Liu C, Lai M, Murabito JM, Levy D, Grove ML, Alonso A, Gibbs R, Dugan-Perez S, Gondek LP, Guallar E, Arking DE. *Co-first author. Nature Communications, 2023. |
Revealing secrets of human genetic variation with population databases.
Lake NJ‡. ‡Corresponding author. Nature Reviews Genetics, 2025. |
Reversible compromise of physiological resilience by accumulation of heteroplasmic mtDNA mutations.
Huang H, Wang Y, Zsengeller ZK, Gorham JM, Vemireddy V, Clark AJ, Pan H, Dreyfuss JM, Jotwani V, Shlipak MG, Sarnak MJ, Parikh CR, Thiessen-Philbrook H, Katz R, Waikar SS, Lake NJ, Lek M, Shi W, Puiu D, Hong YS, Seidman JG, Arking DE, Parikh SM. Science, 2025. |
Mitochondrial DNA variant detection in over 6,500 rare disease families by the systematic analysis of exome and genome sequencing data resolves undiagnosed cases.
Stenton SL, Laricchia K, Lake NJ, Chaluvadi S, Ganesh V, DiTroia S, Osei-Owusu I, Pais L, O'Heir E, Austin-Tse C, O'Leary M, Abu Shanap M, Barrows C, Berger S, Bönnemann CG, Bujakowska KM, Campagna DR, Compton AG, Donkervoort S, Fleming MD, Gallacher L, Gleeson JG, Haliloglu G, Pierce EA, Place EM, Sankaran VG, Shimamura A, Stark Z, Tan TY, Thorburn DR, White SM, Zaki MS; Genomics Research to Elucidate the Genetics of Rare diseases (GREGoR) Consortium; Vilain E, Lek M, Rehm HL, O'Donnell-Luria A. Human Genetics and Genomics Advances, 2025. |
A contextual genomic perspective on physical activity and its relationship to health, well being and illness.
Galimberti M, Levey DF, Deak JD, Adhikari K, Overstreet C, Gupta P, Nitin R, Zhou H, Lake NJ, Harrington KM, Djousse L, Davis LK; VA Million Veteran Program; Gaziano JM, Stein MB, Gelernter J. Nature Genetics, 2025. |
Untargeted proteomics enables ultra-rapid variant prioritization in mitochondrial and other rare diseases.
Hock DH, Caruana NJ, Semcesen LN, Lake NJ, Formosa LE, Amarasekera SSC, Stait T, Tregoning S, Frajman LE, Bournazos AM, Robinson DRL, Ball M, Reljic B, Ryder B, Wallis MJ, Vasudevan A, Beck C, Peters H, Lee J, Tan NB, Freckmann ML; MitoMDT Diagnostic Network for Genomics and Omics; Karlaftis V, Attard C, Monagle P, Samarasinghe A, Brown R, Bi W, Lek M, McFarland R, Taylor RW, Ryan MT, Cooper ST, Stark Z, Christodoulou J, Compton AG, Thorburn DR, Stroud DA. . Genome Medicine, 2025. |
Pathogenic UNC13A variants cause a neurodevelopmental syndrome by impairing synaptic function.
Asadollahi R, Ahmad A, Boonsawat P, Shahanoor Z, Lohse M, Bouazza-Arostegui B, Sun S, Utesch T, Sommer JD, Ilic D, Padmanarayana M, Fischermanns K, Ranjan M, Boll M, Ka C, Piton A, Mattioli F, … Lake NJ, … Kühn AA, Thoms S, Morrie RD, Mekhoubad S, Green EM, Barmada SJ, Gitler AD, Jahn O, Rhee JS, Rosenmund C, Mitkovski M, Sticht H, Sun H, Le Gac G, Taschenberger H, Brose N, Dittman JS, Rauch A, Lipstein N. Nature Genetics, 2025. |
Phenotype Spectrum of TRPM3-Associated Disorders
Jolitz L, Helbig I, Fitzgerald MP, McKeown Ruggiero S, Cohen S, Angelini C, Vallespin E, Michaud V, Gerasimenko A, Cogne B, Isidor B, Keren B, Dyment D, Heron D, Karstensen HG, Cuppen I, Christodoulou J, Wilson M, Lake NJ, Biskup S, Syrbe S, Mori T, Becker LL, Kaindl AM. Annals of Neurology, 2025. |
Saturation mutagenesis-reinforced functional assays for disease-related genes
Ma K, Huang S*, Ng KK*, Lake NJ, Joseph S, Xu J, Lek A, Ge L, Woodman KG, Koczwara KE, Cohen J, Ho V, O'Connor CL, Brindley MA, Campbell KP, Lek M. *Co-second author. Cell, 2024. |
Mitochondrial heteroplasmy improves risk prediction for myeloid neoplasms.
Hong YS*, Pasca S*, Shi W, Puiu D, Lake NJ, Lek M, Ru M, Grove M, Prizment A, Joshu CE, Platz EA, Guallar E, Arking DE, Gondek LP. *Co-first author. Nature Communications, 2024. |
Epigenome-wide Association Analysis of Mitochondrial Heteroplasmy Provides Insight into Molecular Mechanisms of Disease.
Lai M, Kim K, Zheng Y, Castellani CA, Ratliff SM, Wang M, Liu X, Haessler J, Huan T, Bielak LF, Zhao W, Joehanes R, Ma J, Guo X, Manson JE, Grove ML, Bressler J, Taylor KD, Lappalainen T, Kasela S, Blackwell TW, Lake NJ, Faul JD, Ferrier KR, Hou L, Kooperberg C, Reiner AP, Zhang K, Peyser PA, Fornage M, Boerwinkle E, Raffield LM, Carson AP, Rich SS, Liu Y, Levy D, Rotter JI, Smith JA, Arking DE, Liu C; NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium. medRxiv, 2024 |
The Australian Genomics Mitochondrial Flagship: A National Program Delivering Mitochondrial Diagnoses.
Rius R*, Compton AG*, Baker NL, Balasubramaniam S, Best S, Bhattacharya K, Boggs K, Boughtwood T, Braithwaite J, Bratkovic D, Bray A, Brion M, Burke J, Casauria S, Chong B, Coman D, Cowie S, Cowley M, de Silva MG, Delatycki MB, Edwards S, Ellaway C, Fahey MC, Finlay K, Fletcher J, Frajman LE, Frazier AE, Gayevskiy V, Ghaoui R, Goel H, Goranitis I, Haas M, Hock DH, Howting D, Jackson MR, Kava MP, Kemp M, King-Smith S, Lake NJ, Lamont PJ, Lee J, Long JC, MacShane M, Madelli EO, Martin EM, Marum JE, Mattiske T, McGill J, Metke A, Murray S, Panetta J, Phillips LK, Quinn MCJ, Ryan MT, Schenscher S, Simons C, Smith N, Stroud DA, Tchan MC, Tom M, Wallis M, Ware TL, Welch AE, Wools C, Wu Y, Christodoulou J, Thorburn DR. *Co-first author. Genetics in Medicine, 2024. |
Upregulation versus loss of function of NTRK2 in 44 affected individuals leads to 2 distinct neurodevelopmental disorders.
Berger E, Jauss RT, Ranells JD, Zonic E, von Wintzingerode L, Wilson A, Wagner J, Tuttle A, Thomas-Wilson A, Schulte B, Rabin R, Pappas J, Odgis JA, Muthaffar O, Mendez-Fadol A, Lynch M, Levy J, Lehalle D, Lake NJ, Krey I, Kozenko M, Knierim E, Jouret G, Jobanputra V, Isidor B, Hunt D, Hsieh TC, Holtz AM, Haack TB, Gold NB, Dunstheimer D, Donge M, Deb W, De La Rosa Poueriet KA, Danyel M, Christodoulou J, Chopra S, Callewaert B, Busche A, Brick L, Bigay BG, Arlt M, Anikar SS, Almohammal MN, Almanza D, Alhashem A, Bertoli-Avella A, Sticht H, Abou Jamra R. Upregulation versus loss of function of NTRK2 in 44 affected individuals leads to 2 distinct neurodevelopmental disorders. Genetics in Medicine, 2024. |
Multi-omics identifies large mitoribosomal subunit instability caused by pathogenic MRPL39 variants as a cause of pediatric onset mitochondrial disease.
Amarasekera S*, Hock DH*, Lake NJ, Calvo SE, Grønborg SW, Krzesinski EI, Amor DJ, Fahey MC, Simons C, Wibrand F, Mootha VK, Lek M, Lunke S, Stark Z; Østergaard E, Christodoulou J, Thorburn DR, Stroud DA, Compton AG. *Co-first author. Human Molecular Genetics, 2023. |
Estimating the prevalence of LAMA2 congenital muscular dystrophy using population genetic databases.
Lake NJ, Phua J, Liu W, Moors T, Axon S, Lek M. Journal of Neuromuscular Diseases, 2023. |
Neuromuscular disorders: finding the missing genetic diagnoses.
Koczwara KE*, Lake NJ*, DeSimone AM, Lek M. *Co-first author. Trends in Genetics, 2022. |
Centers for Mendelian Genomics: A decade of facilitating gene discovery.
Baxter SM, Posey JE, Lake NJ, Sobreira N, Chong JX, Buyske S, Blue EE, Chadwick LH, Coban-Akdemir ZH, Doheny KF, Davis CP, Lek M, Wellington C, Jhangiani SN, Gerstein M, Gibbs RA, Lifton RP, MacArthur DG, Matise TC, Lupski JR, Valle D, Bamshad MJ, Hamosh A, Mane S, Nickerson DA, Centers for Mendelian Genomics Consortium, Rehm HL, O’Donnell-Luria A. Genetics in Medicine, 2022. |
Fatal perinatal mitochondrial cardiac failure caused by recurrent de novo duplications in the ATAD3 locus.
Frazier AE, Compton AG, Kishita Y, Hock DH, Welch AE, Amarasekera SSC, Rius R, Formosa LE, Imai-Okazaki A, Francis D, Wang M, Lake NJ, Tregoning S, Jabbari JS, Lucattini A, Nitta K, Ohtake A, Murayama A, Amor DJ, McGillivray G, Wong FY, van der Knaap MS, Vermeulen J, Wiltshire EJ, Fletcher JM, Lewis B, Baynam G, Ellaway C, Balasubramaniam S, Wilson MJ, Bhattacharya K, Freckmann M, Arbuckle S, Rodriguez M, Taft RJ, Sadedin S, Cowley MJ, Minoche AE, Calvo SE, Mootha VK, Ryan MT, Okazaki Y, Stroud DA, Simons C, Christodoulou J, Thorburn DR. Med by Cell, 2021. |
Homozygous nonsense variants in two Leigh syndrome disease genes: Distinguishing a dual diagnosis from a hypomorphic protein-truncating variant.
Lake NJ, Formosa LE, Stroud DA, Ryan MT, Calvo SE, Mootha VK, Morar B, Procopis PG, Christodoulou J, Compton AG, Thorburn DR. Human Mutation, 2019. |
Estimating prevalence for limb-girdle muscular dystrophy based on public sequencing databases.
Liu W, Pajusalu S*, Lake NJ*, Zhou G, Ioannidis N, Mittal P, Johnson NE, Weihl CC, Williams BA, Albrecht DE, Rufibach LE, Lek M. *Co-second author. Genetics in Medicine, 2019. |
Leigh syndrome caused by mutations in MTFMT is associated with a better prognosis.
Hayhurst H, de Coo IFM, Piekutowska-Abramczuk D, Alston CL, Sharma S, Thompson K, Rius R, Langping H, Hopton S, Ploski R, Ciara E, Lake NJ, Compton AG, Delatycki MB, Verrips A, Bonnen PE, Jones S, Morris AA, Shakespeare D, Christodoulou J, Wesol-Kucharska D, Rokicki D, Smeets HJM, Pronicka E, Thorburn DR, Gorman GS, McFarland R, Taylor RW, Ng YS. Annals of Clinical and Translational Neurology. 2019 |
Severe leukoencephalopathy with clinical recovery caused by recessive BOLA3 mutations.
Stutterd CA, Lake NJ, Peters H, Lockhart P, Taft RJ, van der Knaap MS, Vanderver A, Thorburn DR, Simons C, Leventer RJ. Journal of Inherited Metabolic Disease Reports, 2019. |
TRAK2, a novel regulator of ABCA1 expression, cholesterol efflux and HDL biogenesis.
Lake NJ, Taylor RL, Trahair H, Harikrishnan KN, Curran JE, Almeida M, Kulkarni H, Mukhamedova N, Hoang A, Low H, Murphy AJ, Johnson MP, Dyer TD, Mahaney MC, Göring HHH, Moses EK, Sviridov D, Blangero J, Jowett JBM, Bozaoglu K. European Heart Journal, 2017. |
Biallelic mutations in MRPS34 lead to instability of the small mitoribosomal subunit and Leigh syndrome.
Lake NJ*, Webb BD*, Stroud DA*, Richman TR*, Ruzzenente B, Compton AG, Mountford HS, Pulman J, Zangarelli C, Rio M, Bodaert N, Assouline Z, Sherpa MD, Schadt EE, Houten SM, Byrnes J, McCormick EM, Zolkipli-Cunningham Z, Zhang Z, Retterer K, Bai R, Calvo SE, Mootha VK, Christodoulou J, Rötig A, Filipovska A, Cristian I, Falk MJ, Metodiev MD, Thorburn DR. *Co-first author. American Journal of Human Genetics, 2017. |
ATAD3 gene cluster deletions cause cerebellar dysfunction associated with altered mitochondrial DNA and cholesterol metabolism.
Desai R, Frazier AE, Durigon R, Patel H, Jones AW, Dalla Rosa I, Lake NJ, Compton AG, Mountford HS, Tucker EJ, Mitchell ALR, Jackson D, Sesay A, Di Re M, van den Heuvel LP, Burke D, Francis D, Lunke S, McGillivray G, Mandelstam S, Mochel F, Keren B, Jardel C, Turner AM, Ian Andrews P, Smeitink J, Spelbrink JN, Heales SJ, Kohda M, Ohtake A, Murayama K, Okazaki Y, Lombès A, Holt IJ, Thorburn DR, Spinazzola A. Brain, 2017. |
Whole exome sequencing identifies the genetic basis of late-onset Leigh syndrome in a patient with MRI but little biochemical evidence of a mitochondrial disorder.
Nafisinia M, Guo Y, Dang X, Li J, Chen Y, Zhang J, Lake NJ, Gold WA, Riley LG, Thorburn DR, Keating B, Xu X, Hakonarson H, Christodoulou J. Journal of Inherited Metabolic Disease Reports. 2017. |
Leigh syndrome: One disease, more than 75 monogenic causes.
Lake NJ, Compton AG, Rahman S, Thorburn DR. Annals of Neurology, 2016. |
Leigh syndrome: Neuropathology and Pathogenesis.
Lake NJ‡*, Bird MJ*, Isohanni P, Paetau A. ‡Corresponding author. *Co-first author. Journal of Neuropathology and Experimental Neurology, 2015. |
Approaches for Dissection of the Genetic Basis of Complex Disease Development in Humans.
Lake NJ, Bozaoglu K, Khan AW, Jowett JBM. Genetic Diversity, 2012 (Book Chapter). |
