Chromosomal abnormalities; Development of novel technologies; Canine genomics
Until recently, my research focused on the chromosomal basis (cytogenetics) of genetic disease. This included research projects on clinical cytogenetics, translocation malsegragation, uniparental disomy and genomic imprinting, mechanisms of chromosomal rearrangements, and development of molecular cytogenetic diagnostic technologies. My laboratory used a variety of chromosomal rearrangements to understand how chromosomes break, stabilize, form translocations, or malsegregate. My research was also concerned with how the genetic imbalance has consequences for the individual and we were involved in identifying genes that cause the phenotypic abnormalities associated with certain chromosomal syndromes.
My current research focus is on the development of high-throughput technologies to advance molecular diagnostics, population genetics of genomic diseases in canines, the identification of novel mutations contributing to inherited diseases in dogs and copy number variation in canines.
Overhoff J, Rabideau MM, Bird LM, Schweitzer DN, Haynes K, Schultz RA, Shaffer LG, Rosenfeld JA, Ellison JW (2014) Refinement of the 8q22.1 microdeletion critical region associated with Nablus mask-like facial syndrome. Am J. Med Genet A. 164:259-263.
Ellison JW, Rosenfeld JA, Shaffer LG (2013) Genetic basis of intellectual disability. Annu. Rev. Med. 64:441-450.
Handrigan GR, Chitavat D, Lionel AC, Pinsk M, Vaags AK, Marshall CR, Dyack S, Escobar LF, Fernandez BA, Stegman JC, Rosenfeld JA, Shaffer LG, Goodenberger M, Hodge JC, Cain JE, Babul-Hirji R, Stavropoulos DJ, Yiu V, Scherer SW, Rosenblum ND (2013) deletions in 16q24.2 are associated with autism spectrum disorder, intellectual disability and congenital renal malformation. J. Med. Gent. 50:163-173.
Lindgren AM, Hoyos T, Talkowski ME, Hanscom C, Blumenthal I, Chiang C, Ernst C, Pereira S, Ordulu Z, Clericuzio C, Drautz JM, Rosenfeld JA, Shaffer LG, Velsher L, Pynn T, Vermeesch J, Harris dJ, Gusella JF, Liao EC, Morton CC (2013) Haploinsufficiency of KDM6A is associated with severe psychomotor retardation, global growth restriction, seizures and cleft palate. Hum Gent. 132:537-552.
Nguyen LS, Kim HG, Rosenfeld JA, Shen Y, Gusella JF, Lacassie Y, Layman LC, Shaffer LG, Gécz J (2013) Contribution of copy number variants involving nonsense-mediated mRNA decay pathway genes to neuro-developmental disorders. Hum. Mol. Genet. 22:1816-1825.
Paciorkowski AR, Traylor RN, Rosenfend JA, Hoover JM, Harris CJ, Winter S, Lacassie Y, Bialer M, Lamg AN, Schultz RA, Berry-Kravis E, Porter BE, Falk M, Vankat A, Vanzo RJ, Cohen JS, Fatemi A, Dobyns WB, Shaffer LG, Ballif BC, Marsh ED (2013) MEF2C haploinsufficiency features consistent hyperdinesis, variable epilepsy, and has a role in dorsal and ventral neuronal developmental pathways. Neurogenetics, 14:99-111.
Dabell MP, Rosenfeld JA, Bader P, Escobar LF, El-Kechen D, Vallee SE, Dinulos MB, Curry C, Cisher J, Tervo R, Hannibal MC, Siefkas K, Wyatt PR, Hughes L, Smith R, Ellingwood S, Lacassie Y, Stroud T, Farrell SA, Sanchez0Lara PA, Randolph LM, Niyazov D, Stevens CA, Schoonveld C, Skidmore D, Mackay S, Miles JH, Moodley M, Huillet A, Neill NJ, Ellison JW, Ballif BC, Shaffer LG (2013) Investigation of NRXN1 deletions: Clinical and molecular characterization. Am. J. Med. Genet. A. 161:717-731.
Rosenfeld JA, Kim KH, Angle B, Troxell R, Gofski JL, Westemeyer M, Frydman M, Senturias Y, Earl D, Torchia B, Schulta RA, Ellison JW, Tsuchiya K, Zimmerman S, Smolarek TA, Ballif BC, Shaffer LG (2013) Further Evidence of Contrasting Phenotypes Caused by Reciprocal Deletions and Duplications: Duplication of NSD1 Causes Growth Retardation and Microcephaly. Mol. Syndromol. 3:247-254.
Hirata H, Nanda I, van Riesen A, McMichael G, Hu H, Hambrock M, Papon MA, fischer U, Marouillat S, Ding C, Alirol S, Bienek M, Preisler-Adams S, Grimme A, Seelow D, Webster R, Haan E, MacLennan A, Stenzel W, Yap TY, Gardner A, Nguyen LS, Shaw M, Lebrun N, Haas SA, Kress W, Haaf T, Schellenberger E, Chelly J, Viot G, Shaffer LG, Rosenfeld JA, Kramer N, Falk R, El-Khechen D, Escobar LF, Hennekam R, Wieacker P, Hübner C, Ropers HH, Gecz J, Schuelke M, Laumonnier F, Kalscheuer VM (2013) ZC4H2 mutations are associated with arthrogryposis multiplex congenital and intellectual disability through impairment of central and peripheral synaptic plasticity. Am. J. Hum. Genet. 92:681-695.
Curry CJ, Rosenfeld JA, Grant E, Gripp KW, Anderson C, Aylsworth AS, Saad TB, Chizhikov VV, Dybose G, Fagerberg C, Falco M, Fels C, Fichera M, Graakjaer J, Greco D, Hair J, Hopkins E, Huggins M, Ladda R, Li C, Moeschler J, Nowaczyk MJM, Ozmore JR, Reitano S, Romano C, Roos L, Schnure RE, Sell S, Suwannarat P, Svaneby D, Szybowska M, Tarnopolsky M, Tervo R, Tsai AC-H, Tucker M, Vallee S, Wheeler FC, Zand DJ, Barkovich JA, Aradhya S, Shaffer LG, Dobyns WB (2013) The duplication 17p13.3 phenotype: Analysis of 21 families delineates developmental, behavioral and brain abnormalities, and rare variant phenotypes. Am. J. Med. Genet A. 161A:1833-1852.
Shuvarikov A, Campbell IM, Dittwald P, Neill NJ, Bialer MG, Moore C, Wheeler PG, Wallace SE, Hannibal MC, Murray MF, Giovanni MA, Terespolsky D, Sodhi S, Cassina M, Viskochil D, Moghaddam B, Herman K, Brown C, Gambin A, Cheung SW, Patel A, Lamb AN, Shaffer LG, Ellison JW, Ravnan JB, Stankiewicz P, Rosenfeld JA (2013) Recurrent HERV-H-mediated 3q13.2-q13.31 deletions cause a syndrome of hypotonia and motor, language, and cognitive delays, Hum Mutat. 34:1415-1423.
Shaffer LG, Rosenfeld JA (2013) Microarray-based prenatal diagnosis for the identification of fetal chromosome abnormalities. Expert Rev Mol Diagn. 13:601-611.
Goldlust IS, Hermetz KE, Catalano LM, Barfield RT, Cozad R, Wynn G, Ozdemir AC, Conneely KN, Mulle JG, Dharamrup S, Hegde MR, Kim KH, Angle B, Colley A, Webb AE, Thorland EC, Ellison JW, Rosenfeld JA, Ballif BC, Shaffer LG, Demmer LA; Unique Rare Chromosome Disorder Support Group, Rudd MK (2013) Mouse model implicates GNB3 duplication in a childhood obesity syndrome. Proc Natl Acad Sci USA. 110:14990-14994.
Callaway JL, Shaffer LG, Chitty L, Rosenfeld JA, Crolla JA (2013) The clinical utility of microarray technologies applies to prenatal cytogenetics in the presence of a normal conventional karyotype: a review of the literature. Prenat Diagn. 23:1-5.
Carey AS, Liang L, Edwards J, Brandt T, Mei H, Sharp AJ, Hsu DT, Newburger JW, Ohve RG, Chung WK, Russell MW, Rosenfeld JA, Shaffer LG, Parides MK, Edelmann L, Gelb BD (2013) The impact of CNVs on outcomes for infants with single ventricle heart defects. Circ Cardiovasc Genet. 6:444-451.
Shiba N, Daza RA, Shaffer LG, Barkovich AJ, Dobyns WB, Hevner RF (2013) Neuropathology of brain and spinal malformations in a case of monosomy 1p36. Acta Neuropathol Commun. 1:45-58.
Rosenfeld JA, Coe BP, Eichler EE, Cuckle H, Shaffer LG (2012). Estimates of penetrance for recurrent pathogenic copy-number variations. Gent. Med. 15:478-481.
Gajecka, M., A.J. Gentles, A. Tsai, D. Chitayat, K.L. Mackay, C.D. Glotzbach, M.R. Lieber, and L.G. Shaffer, Unexpected complexity at breakpoint junctions in phenotypically normal individuals and mechanisms involved in generating balanced translocations t(1;22)(p36;q13). Genome Res, 2008. 18(11): p. 1733-42.
Gajecka, M., R. Saadeh, K.L. Mackay, C.D. Glotzbach, K. Spodar, D. Chitayat, and L.G. Shaffer, Clinical and molecular cytogenetic characterization of four patients with unbalanced translocation der(1)t(1;22)(p36;q13). Am J Med Genet A, 2008. 146A(21): p. 2777-84.
Gajecka, M., K.L. Mackay, and L.G. Shaffer, Monosomy 1p36 deletion syndrome. Am J Med Genet C Semin Med Genet, 2007. 145C(4): p. 346-56.
Jarmuz, M., C.D. Glotzbach, K.A. Bailey, R. Bandyopadhyay, and L.G. Shaffer, The Evolution of satellite III DNA subfamilies among primates. Am J Hum Genet, 2007. 80(3): p. 495-501.
Shaffer, L.G., A. Theisen, B.A. Bejjani, B.C. Ballif, A.S. Aylsworth, C. Lim, M. McDonald, J.W. Ellison, D. Kostiner, S. Saitta, and T. Shaikh, The discovery of microdeletion syndromes in the post-genomic era: review of the methodology and characterization of a new 1q41q42 microdeletion syndrome. Genet Med, 2007. 9(9): p. 607-16.
Gajecka, M., C.D. Glotzbach, M. Jarmuz, B.C. Ballif, and L.G. Shaffer, Identification of cryptic imbalance in phenotypically normal and abnormal translocation carriers. Eur J Hum Genet, 2006. 14(12): p. 1255-62.
Gajecka, M., C.D. Glotzbach, and L.G. Shaffer, Characterization of a complex rearrangement with interstitial deletions and inversion on human chromosome 1. Chromosome Res, 2006. 14(3): p. 277-82.
Gajecka, M., A. Pavlicek, C.D. Glotzbach, B.C. Ballif, M. Jarmuz, J. Jurka, and L.G. Shaffer, Identification of sequence motifs at the breakpoint junctions in three t(1;9)(p36.3;q34) and delineation of mechanisms involved in generating balanced translocations. Hum Genet, 2006. 120(4): p. 519-26.
Jarmuz, M., B.C. Ballif, C.D. Kashork, A.P. Theisen, B.A. Bejjani, and L.G. Shaffer, Comparative genomic hybridization by microarray for the detection of cytogenetic imbalance. Methods Mol Med, 2006. 128: p. 23-31.
Jarmuz, M. and L.G. Shaffer, Cytogenetic analysis of cardiovascular disease: karyotyping. Methods Mol Med, 2006. 128: p. 1-9.
Shaffer, L.G., Risk estimates for uniparental disomy following prenatal detection of a nonhomologous Robertsonian translocation. Prenat Diagn, 2006. 26(4): p. 303-7.
Gajecka M, Glotzbach CD, Shaffer LG (2006) Characterization of a complex rearrangement with interstitial deletions and inversion on human chromosome 1. Chrom Res 14:277-282.
Shaffer LG, Bejjani BA (2006) Medical Applications of Array CGH and the Transformation of Clinical Cytogenetics. Cytogen Genome Res (in press).
Bejjani BA, Shaffer LG (2006) Application of array-based comparative genomic hybridization to clinical diagnostics. J Mol Diagn (in press).
Kashork CD, Theisen A, Bejjani BA, Shaffer LG (2006) Rearrangements of chromosome 18 illustrate the utility of array-based comparative genomic hybridization. Cytogen Genome Res (in press).
Gajecka, M., W. Yu, B.C. Ballif, C.D. Glotzbach, K.A. Bailey, C.A. Shaw, C.D. Kashork, H.A. Heilstedt, D.A. Ansel, A. Theisen, R. Rice, D.P. Rice, and L.G. Shaffer, Delineation of mechanisms and regions of dosage imbalance in complex rearrangements of 1p36 leads to a putative gene for regulation of cranial suture closure. Eur J Hum Genet, 2005. 13(2): p. 139-49.
Rosa, A.L., Y.Q. Wu, B. Kwabi-Addo, K.J. Coveler, V. Reid Sutton, and L.G. Shaffer, Allele-specific methylation of a functional CTCF binding site upstream of MEG3 in the human imprinted domain of 14q32. Chromosome Res, 2005. 13(8): p. 809-18.
Shaffer, L.G., American College of Medical Genetics guideline on the cytogenetic evaluation of the individual with developmental delay or mental retardation. Genet Med, 2005. 7(9): p. 650-4.