My lab has been interested in a variety of cytological phenomena and chromosome structure and function including:  the formation of chromosomal aberrations, a correlation of phenotype and karyotype and a study of centromere structure and function.  We are studying the molecular formation and karyotype-phenotype correlation of two specific chromosomal aberrations; inv dup (15) and deletions of the short arm of chromosome 9 [ del (9p)].  Accessory chromosomes involving an inverted duplication of the proximal region of chromosome 15, although rare, occur frequently enough to be associated with several different phenotypes.  It has not been established whether these all occur at similar breakpoints and if they are symmetrical or non-symmetrical.  Utilization of cytogenetic and molecular techniques along with delineation of DNA sequence in proximal 15q will allow for delineation of these breakpoints.  This methodology will also allow for the subgrouping of patients with 9p deletions, not possible by conventional banding techniques.  Our studies to date with 9p deletion patients have revealed a 500 kb segment, which is the critical region for the 9p deletion syndrome, and we are initiating a study of genes in this region.  In addition our preliminary studies have revealed that specific repetitive sequences (LINES and SINES) are involved in the formation of the 9p deletions.  Additional studies will allow molecular classification of both the deletion 9p syndrome and inv dup (15) and will provide precise correlation between the patients’ phenotype and genotype.

My laboratory is also interested in studying centromere structure and function.  These studies have involved examination of two types of centromere aberrations; those with two centromeric regions (dicentric) and those without a classical centromeric region (acentric).  This work involves the delineation of the reasons for centromere inactivation in dicentrics and centromere activation in acentric chromosomes.  We currently have created a BAC map of an acentric chromosome derived from chromosome 9 and have delineated a 350kb neocentric region.  This sequence has been examined to allow a better understanding of the neocentric activity, revealing an increased AT frequency and elevated LTR level.  Further studies are currently in progress with other neocentric regions.

Selected Publications

Wandstrat AE, Leana-Cox J, Jenkins L, Schwartz S.  Molecular cytogenetic evidence for a common breakpoint in large (Class III) inverted duplications of chromosome 15.  Am J Hum Genet 62:925-36, 1998.

Christ LA, Crowe CA, Micale MA, Conroy JM, Schwartz S.  Chromosome breakage hotspots and delineation of the critical region for the 9p-deletion syndrome.  Am J Hum Genet 65:1387-1395, 1999.

Sirko-Osadsa DA, Cassidy SB, Depinet TW, Robin NH, Limwongse C, Schwartz S.  Molecular refinement of karyotype:  Beyond the cytogenetic band.  Genetics in Medicine 1:254-261, 1999.

Wandstrat AE, Schwartz S.  Isolation and molecular analysis of inv dup(15) and construction of a physical map of a common breakpoint in order to elucidate their mechanism of formation.  Chromosoma 109:498-505, 2000. 

Satinover DL, Vance GH, Van Dyke DL and Schwartz S: Cytogenetic analysis and construction of a BAC contig across a common neocentromeric region from 9p.  Chromosoma 110:275-283, 2001. 

Bailey JA, Gu Z, Clark RA, Reinert K, Samonte RV, Schwartz S, Adams MD, Myers EW, Li PW and Eichler EE: Recent segmental duplications of the human genome.  Science 296(5576):2222-2225, 2002. 

Rudd, MK, Mays RW, Schwartz S and Willard HF:  Human artificial chromosomes with alpha satellite based de novo centromeres show increased frequency of nondisjunction and anaphase lag.  Genome Research 23:7689-7697, 2003

Locke D, Segraves R, Nicholls R, Schwartz S, Pinkel D, Albertson D, Eichler EE: BAC microarray analysis of 15q11-q13 rearrangements and the impact of segmental duplications.  J Med Genetics 41:175-182, 2004.

Astbury C, Christ L, Aughton D, Cassidy S, Kumar A, Eichler E and Schwartz S: Detection of cryptic deletions in de novo ‘balanced’ chromosome rearrangements: further evidence for their role in phenotypic abnormalities.  Gen Medicine 6:81-89, 2004.

Astbury C, Christ LA, Aughton DJ, Cassidy SB, Fujimoto A, Pletcher IA , Schafer IA and Schwartz S: Delineation of complex chromosomal rearrangements: evidence for increased complexity.  Hum Genetics 114:448-457, 2004.

She X, Horvath JE, Jiang Z, Liu G, Furey TS, Christ L, Clark R, Graves T, Gulden CL, Alkan C, Bailey JA, Sahinalp C, Rocchi M, Haussler D, Wilson RK, Miller W, Schwartz S, and Eichler EE:  The structure and evolution of centromeric transition regions within the human genome.  Nature 430:857-864, 2004.