James R. Lupski

Mechanisms for human genomic rearrangements (2008)

Gu, Wenli, Zhang, Feng, Lupski, James R

Abstract Genomic rearrangements describe gross DNA changes of the size ranging from a couple of hundred base pairs, the size of an average exon, to megabases (Mb). When greater than 3 to 5 Mb, such...

Population Bottlenecks as a Potential Major Shaping Force of Human Genome Architecture (2007)

Adrian Gherman, Peter E. Chen, Tanya M. Teslovich, Pawel Stankiewicz, Marjorie Withers, Carl S. Kashuk, ...

The modern synthetic view of human evolution proposes that the fixation of novel mutations is driven by the balance among selective advantage, selective disadvantage, and genetic drift. When...

Population Bottlenecks as a Potential Major Shaping Force of Human Genome Architecture (2007)

Adrian Gherman, Peter E. Chen, Tanya Teslovich, Pawel Stankiewicz, Marjorie Withers, Carl S Kashuk, ...

The modern synthetic view of human evolution proposes that the fixation of novel mutations is driven by the balance between selective advantage, selective disadvantage and genetic drift. When...

Genomic Disorders: Molecular Mechanisms for Rearrangements and Conveyed Phenotypes (2005)

James R. Lupski, Pawel Stankiewicz

Rearrangements of our genome can be responsible for inherited as well as sporadic traits. The analyses of chromosome breakpoints in the proximal short arm of Chromosome 17 (17p) reveal nonallelic...

Hotspots of homologous recombination in the human genome: not all homologous sequences are equal (2004)

Lupski, James R

Abstract Homologous recombination between alleles or non-allelic paralogous sequences does not occur uniformly but is concentrated in 'hotspots' with high recombination rates. Recent studies of these...

Interstitial deletion 9q22.32-q33.2 associated with additional familial translocation t(9;17)(q34.11;p11.2) in a patient with Gorlin-Goltz syndrome and features of Nail-patella syndrome (2004)

Midro,Alina T., Panasiuk,Barbara, Tümer,Zeynep, Stankiewicz,Pawel, Silahtaroglu,Asli, Lupski,James R., ...

The phenotype of Gorlin-Goltz syndrome or basal cell nevus syndrome (BCNS, #109400, OMIM), a Mendelian trait due to PTCH mutations has been reported in a few cases of interstitial deletion of...

Animal models for human contiguous gene syndromes and other genomic disorders (2004)

Walz,Katherina, Fonseca,Patricia, Lupski,James R.

Genomic disorders refer to a group of syndromes caused by DNA rearrangements, such as deletions and duplications, which result in an alteration of normal gene dosage. The chromosomal rearrangements...

Interstitial deletion 9q22.32-q33.2 associated with additional familial translocation t(9;17)(q34.11;p11.2) in a patient with Gorlin-Goltz syndrome and features of Nail-patella syndrome (2004)

Midro, Alina T., Panasiuk, Barbara, Tümer, Zeynep, Stankiewicz, Pawel, Silahtaroglu, Asli, Lupski, James R., ...

The phenotype of Gorlin-Goltz syndrome or basal cell nevus syndrome (BCNS, #109400, OMIM), a Mendelian trait due to PTCH mutations has been reported in a few cases of interstitial deletion of...

Fliih, a Gelsolin-Related Cytoskeletal Regulator Essential for Early Mammalian Embryonic Development (2002)

Campbell, Hugh D., Fountain, Shelley, McLennan, Ian S., Berven, Leise A., Crouch, Michael Francis, Davy, Deborah A., ...

The Drosophila melanogaster flightless I gene is required for normal cellularization of the syncytial blastoderm. Highly conserved homologues of flightless I are present in Caenorhabditis elegans,...

Fliih, a Gelsolin-Related Cytoskeletal Regulator Essential for Early Mammalian Embryonic Development (2002)

Campbell, Hugh D., Fountain, Shelley, McLennan, Ian S., Berven, Leise A., Crouch, Michael Francis, Davy, Deborah A., ...

The Drosophila melanogaster flightless I gene is required for normal cellularization of the syncytial blastoderm. Highly conserved homologues of flightless I are present in Caenorhabditis elegans,...

Molecular Epidemiological Analysis of the Changing Nature of a Meningococcal Outbreak following a Vaccination Campaign

Shlush, Liran I., Behar, Doron M., Zelazny, Adrian, Keller, Nathy, Lupski, James R., Beaudet, Arthur L., ...

A serogroup C meningococcal outbreak that occurred in an Israeli Arab village led to a massive vaccination campaign. During the subsequent 18 months, new cases of type B Neisseria meningitidis...

Fliih, a Gelsolin-Related Cytoskeletal Regulator Essential for Early Mammalian Embryonic Development

Campbell, Hugh D., Fountain, Shelley, McLennan, Ian S., Berven, Leise A., Crouch, Michael F., Davy, Deborah A., ...

The Drosophila melanogaster flightless I gene is required for normal cellularization of the syncytial blastoderm. Highly conserved homologues of flightless I are present in Caenorhabditis elegans,...

A computational/functional genomics approach for the enrichment of the retinal transcriptome and the identification of positional candidate retinopathy genes

Katsanis, Nicholas, Worley, Kim C., Gonzalez, Guillermo, Ansley, Stephen J., Lupski, James R.

Grouping genes by virtue of their sequence similarity, functional association, or spatiotemporal distribution is an important first step in investigating function. Given the recent identification of...

Modeling del(17)(p11.2p11.2) and dup(17)(p11.2p11.2) Contiguous Gene Syndromes by Chromosome Engineering in Mice: Phenotypic Consequences of Gene Dosage Imbalance

Walz, Katherina, Caratini-Rivera, Sandra, Bi, Weimin, Fonseca, Patricia, Mansouri, Dena L., Lynch, Jennifer, ...

Contiguous gene syndromes (CGS) are a group of disorders associated with chromosomal rearrangements of which the phenotype is thought to result from altered copy numbers of physically linked...

Genes in a Refined Smith-Magenis Syndrome Critical Deletion Interval on Chromosome 17p11.2 and the Syntenic Region of the Mouse

Bi, Weimin, Yan, Jiong, Stankiewicz, Paweł, Park, Sung-Sup, Walz, Katherina, Boerkoel, Cornelius F., ...

Smith-Magenis syndrome (SMS) is a multiple congenital anomaly/mental retardation syndrome associated with behavioral abnormalities and sleep disturbance. Most patients have the same ∼4 Mb...

Structure and Evolution of the Smith-Magenis Syndrome Repeat Gene Clusters, SMS-REPs

Park, Sung-Sup, Stankiewicz, Paweł, Bi, Weimin, Shaw, Christine, Lehoczky, Jessica, Dewar, Ken, ...

An ∼4-Mb genomic segment on chromosome 17p11.2, commonly deleted in patients with the Smith-Magenis syndrome (SMS) and duplicated in patients with dup(17)(p11.2p11.2) syndrome, is flanked by large,...

COP9 Signalosome Subunit 3 Is Essential for Maintenance of Cell Proliferation in the Mouse Embryonic Epiblast

Yan, Jiong, Walz, Katherina, Nakamura, Hisashi, Carattini-Rivera, Sandra, Zhao, Qi, Vogel, Hannes, ...

Csn3 (Cops3) maps to the mouse chromosome 11 region syntenic to the common deletion interval for the Smith-Magenis syndrome, a contiguous gene deletion syndrome. It encodes the third subunit of an...

Localization of mariner DNA Transposons in the Human Genome by PRINS

Reiter, Lawrence T., Liehr, Thomas, Rautenstrauss, Bernd, Robertson, Hugh M., Lupski, James R.

Homologous recombination occurring among misaligned repeated sequences is a significant source of the molecular rearrangements resulting in human genetic disease. Studies of the Charcot-Marie-Tooth...

The 1.4-Mb CMT1A Duplication/HNPP Deletion Genomic Region Reveals Unique Genome Architectural Features and Provides Insights into the Recent Evolution of New Genes

Inoue, Ken, Dewar, Ken, Katsanis, Nicholas, Reiter, Lawrence T., Lander, Eric S., Devon, Keri L., ...

Duplication and deletion of the 1.4-Mb region in 17p12 that is delimited by two 24-kb low copy number repeats (CMT1A–REPs) represent frequent genomic rearrangements resulting in two common...

The Evolutionary Chromosome Translocation 4;19 in Gorilla gorilla is Associated with Microduplication of the Chromosome Fragment Syntenic to Sequences Surrounding the Human Proximal CMT1A-REP

Stankiewicz, Pawel, Park, Sung-Sup, Inoue, Ken, Lupski, James R.

Many genomic disorders occur as a result of chromosome rearrangements involving low-copy repeats (LCRs). To better understand the molecular basis of chromosome rearrangements, including...

Serial segmental duplications during primate evolution result in complex human genome architecture

Stankiewicz, Paweł, Shaw, Christine J., Withers, Marjorie, Inoue, Ken, Lupski, James R.

The human genome is particularly rich in low-copy repeats (LCRs) or segmental duplications (5%–10%), and this characteristic likely distinguishes us from lower mammals such as rodents. How and why...

Microbial DNA Typing by Automated Repetitive-Sequence-Based PCR

Healy, Mimi, Huong, Joe, Bittner, Traci, Lising, Maricel, Frye, Stacie, Raza, Sabeen, ...

Repetitive sequence-based PCR (rep-PCR) has been recognized as an effective method for bacterial strain typing. Recently, rep-PCR has been commercially adapted to an automated format known as the...

Hotspots of homologous recombination in the human genome: not all homologous sequences are equal

Lupski, James R

Recent studies of homologous recombination hotspots show that they do not share common sequence motifs, but they do have other features in common.

Deficiency in 3′-phosphoglycolate processing in human cells with a hereditary mutation in tyrosyl-DNA phosphodiesterase (TDP1)

Zhou, Tong, Lee, Jae Wan, Tatavarthi, Haritha, Lupski, James R., Valerie, Kristoffer, Povirk, Lawrence F.

Tyrosyl-DNA phosphodiesterase (TDP1) is a DNA repair enzyme that removes peptide fragments linked through tyrosine to the 3′ end of DNA, and can also remove 3′-phosphoglycolates (PGs) formed by...

Periaxin Mutations Cause Recessive Dejerine-Sottas Neuropathy

Boerkoel, Cornelius F., Takashima, Hiroshi, Stankiewicz, Pawel, Garcia, Carlos A., Leber, Steven M., Rhee-Morris, Laila, ...

The periaxin gene (PRX) encodes two PDZ-domain proteins, L- and S-periaxin, that are required for maintenance of peripheral nerve myelin. Prx−/− mice develop a severe demyelinating peripheral...

Genetic and Mutational Analyses of a Large Multiethnic Bardet-Biedl Cohort Reveal a Minor Involvement of BBS6 and Delineate the Critical Intervals of Other Loci

Beales, Philip L., Katsanis, Nicholas, Lewis, Richard A., Ansley, Stephen J., Elcioglu, Nursel, Raza, Jamal, ...

Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disorder characterized primarily by obesity, polydactyly, retinal dystrophy, and renal disease. The significant genetic and clinical...

Delineation of the Critical Interval of Bardet-Biedl Syndrome 1 (BBS1) to a Small Region of 11q13, through Linkage and Haplotype Analysis of 91 Pedigrees

Katsanis, Nicholas, Lewis, Richard A., Stockton, David W., Mai, Phuong M. T., Baird, Lisa, Beales, Philip L., ...

Bardet-Biedl syndrome (BBS) is a genetically heterogeneous recessive disease characterized primarily by atypical retinitis pigmentosa, obesity, polydactyly, hypogenitalism, and mental retardation....

Genomic Disorders: Molecular Mechanisms for Rearrangements and Conveyed Phenotypes

Lupski, James R, Stankiewicz, Pawel

Rearrangements of our genome can be responsible for inherited as well as sporadic traits. The analyses of chromosome breakpoints in the proximal short arm of Chromosome 17 (17p) reveal nonallelic...

Curcumin Treatment Abrogates Endoplasmic Reticulum Retention and Aggregation-Induced Apoptosis Associated with Neuropathy-Causing Myelin Protein Zero–Truncating Mutants

Khajavi, Mehrdad, Inoue, Ken, Wiszniewski, Wojciech, Ohyama, Tomoko, Snipes, G. Jackson, Lupski, James R.

Mutations in MPZ, the gene encoding myelin protein zero (MPZ), the major protein constituent of peripheral myelin, can cause the adult-onset, inherited neuropathy Charcot-Marie-Tooth disease, as well...

Rai1 duplication causes physical and behavioral phenotypes in a mouse model of dup(17)(p11.2p11.2)

Walz, Katherina, Paylor, Richard, Yan, Jiong, Bi, Weimin, Lupski, James R.

Genomic disorders are conditions that result from DNA rearrangements, such as deletions or duplications. The identification of the dosage-sensitive gene(s) within the rearranged genomic interval is...

Molecular Epidemiological Analysis of the Changing Nature of a Meningococcal Outbreak following a Vaccination Campaign

Shlush, Liran I., Behar, Doron M., Zelazny, Adrian, Keller, Nathy, Lupski, James R., Beaudet, Arthur L., ...

A serogroup C meningococcal outbreak that occurred in an Israeli Arab village led to a massive vaccination campaign. During the subsequent 18 months, new cases of type B Neisseria meningitidis...

Fliih, a Gelsolin-Related Cytoskeletal Regulator Essential for Early Mammalian Embryonic Development

Campbell, Hugh D., Fountain, Shelley, McLennan, Ian S., Berven, Leise A., Crouch, Michael F., Davy, Deborah A., ...

The Drosophila melanogaster flightless I gene is required for normal cellularization of the syncytial blastoderm. Highly conserved homologues of flightless I are present in Caenorhabditis elegans,...

A computational/functional genomics approach for the enrichment of the retinal transcriptome and the identification of positional candidate retinopathy genes

Katsanis, Nicholas, Worley, Kim C., Gonzalez, Guillermo, Ansley, Stephen J., Lupski, James R.

Grouping genes by virtue of their sequence similarity, functional association, or spatiotemporal distribution is an important first step in investigating function. Given the recent identification of...

Modeling del(17)(p11.2p11.2) and dup(17)(p11.2p11.2) Contiguous Gene Syndromes by Chromosome Engineering in Mice: Phenotypic Consequences of Gene Dosage Imbalance

Walz, Katherina, Caratini-Rivera, Sandra, Bi, Weimin, Fonseca, Patricia, Mansouri, Dena L., Lynch, Jennifer, ...

Contiguous gene syndromes (CGS) are a group of disorders associated with chromosomal rearrangements of which the phenotype is thought to result from altered copy numbers of physically linked...

Genes in a Refined Smith-Magenis Syndrome Critical Deletion Interval on Chromosome 17p11.2 and the Syntenic Region of the Mouse

Bi, Weimin, Yan, Jiong, Stankiewicz, Paweł, Park, Sung-Sup, Walz, Katherina, Boerkoel, Cornelius F., ...

Smith-Magenis syndrome (SMS) is a multiple congenital anomaly/mental retardation syndrome associated with behavioral abnormalities and sleep disturbance. Most patients have the same ∼4 Mb...

Structure and Evolution of the Smith-Magenis Syndrome Repeat Gene Clusters, SMS-REPs

Park, Sung-Sup, Stankiewicz, Paweł, Bi, Weimin, Shaw, Christine, Lehoczky, Jessica, Dewar, Ken, ...

An ∼4-Mb genomic segment on chromosome 17p11.2, commonly deleted in patients with the Smith-Magenis syndrome (SMS) and duplicated in patients with dup(17)(p11.2p11.2) syndrome, is flanked by large,...

COP9 Signalosome Subunit 3 Is Essential for Maintenance of Cell Proliferation in the Mouse Embryonic Epiblast

Yan, Jiong, Walz, Katherina, Nakamura, Hisashi, Carattini-Rivera, Sandra, Zhao, Qi, Vogel, Hannes, ...

Csn3 (Cops3) maps to the mouse chromosome 11 region syntenic to the common deletion interval for the Smith-Magenis syndrome, a contiguous gene deletion syndrome. It encodes the third subunit of an...

Localization of mariner DNA Transposons in the Human Genome by PRINS

Reiter, Lawrence T., Liehr, Thomas, Rautenstrauss, Bernd, Robertson, Hugh M., Lupski, James R.

Homologous recombination occurring among misaligned repeated sequences is a significant source of the molecular rearrangements resulting in human genetic disease. Studies of the Charcot-Marie-Tooth...

The 1.4-Mb CMT1A Duplication/HNPP Deletion Genomic Region Reveals Unique Genome Architectural Features and Provides Insights into the Recent Evolution of New Genes

Inoue, Ken, Dewar, Ken, Katsanis, Nicholas, Reiter, Lawrence T., Lander, Eric S., Devon, Keri L., ...

Duplication and deletion of the 1.4-Mb region in 17p12 that is delimited by two 24-kb low copy number repeats (CMT1A–REPs) represent frequent genomic rearrangements resulting in two common...

The Evolutionary Chromosome Translocation 4;19 in Gorilla gorilla is Associated with Microduplication of the Chromosome Fragment Syntenic to Sequences Surrounding the Human Proximal CMT1A-REP

Stankiewicz, Pawel, Park, Sung-Sup, Inoue, Ken, Lupski, James R.

Many genomic disorders occur as a result of chromosome rearrangements involving low-copy repeats (LCRs). To better understand the molecular basis of chromosome rearrangements, including...

Genomic Rearrangements Resulting in PLP1 Deletion Occur by Nonhomologous End Joining and Cause Different Dysmyelinating Phenotypes in Males and Females

Inoue, Ken, Osaka, Hitoshi, Thurston, Virginia C., Clarke, Joe T. R., Yoneyama, Akira, Rosenbarker, Lisa, ...

In the majority of patients with Pelizaeus-Merzbacher disease, duplication of the proteolipid protein gene PLP1 is responsible, whereas deletion of PLP1 is infrequent. Genomic mechanisms for these...

Newfoundland Rod-Cone Dystrophy, an Early-Onset Retinal Dystrophy, Is Caused by Splice-Junction Mutations in RLBP1

Eichers, Erica R., Green, Jane S., Stockton, David W., Jackman, Christopher S., Whelan, James, McNamara, J. Arch, ...

Some isolated populations exhibit an increased prevalence of rare recessive diseases. The island of Newfoundland is a characteristic geographic isolate, settled by a small number of families...

BBS4 Is a Minor Contributor to Bardet-Biedl Syndrome and May Also Participate in Triallelic Inheritance

Katsanis, Nicholas, Eichers, Erica R., Ansley, Stephen J., Lewis, Richard Alan, Kayserili, Hülya, Hoskins, Bethan E., ...

Bardet-Biedl syndrome (BBS) is an uncommon multisystemic disorder characterized primarily by retinal dystrophy, obesity, polydactyly, and renal dysfunction. BBS has been modeled historically as an...

Genetic Proof of Unequal Meiotic Crossovers in Reciprocal Deletion and Duplication of 17p11.2

Shaw, Christine J., Bi, Weimin, Lupski, James R.

A number of common contiguous gene syndromes have been shown to result from nonallelic homologous recombination (NAHR) within region-specific low-copy repeats (LCRs). The reciprocal duplications are...

Serial segmental duplications during primate evolution result in complex human genome architecture

Stankiewicz, Paweł, Shaw, Christine J., Withers, Marjorie, Inoue, Ken, Lupski, James R.

The human genome is particularly rich in low-copy repeats (LCRs) or segmental duplications (5%–10%), and this characteristic likely distinguishes us from lower mammals such as rodents. How and why...

Microbial DNA Typing by Automated Repetitive-Sequence-Based PCR

Healy, Mimi, Huong, Joe, Bittner, Traci, Lising, Maricel, Frye, Stacie, Raza, Sabeen, ...

Repetitive sequence-based PCR (rep-PCR) has been recognized as an effective method for bacterial strain typing. Recently, rep-PCR has been commercially adapted to an automated format known as the...

Hotspots of homologous recombination in the human genome: not all homologous sequences are equal

Lupski, James R

Recent studies of homologous recombination hotspots show that they do not share common sequence motifs, but they do have other features in common.

Deficiency in 3′-phosphoglycolate processing in human cells with a hereditary mutation in tyrosyl-DNA phosphodiesterase (TDP1)

Zhou, Tong, Lee, Jae Wan, Tatavarthi, Haritha, Lupski, James R., Valerie, Kristoffer, Povirk, Lawrence F.

Tyrosyl-DNA phosphodiesterase (TDP1) is a DNA repair enzyme that removes peptide fragments linked through tyrosine to the 3′ end of DNA, and can also remove 3′-phosphoglycolates (PGs) formed by...

Identification of a Novel Bardet-Biedl Syndrome Protein, BBS7, That Shares Structural Features with BBS1 and BBS2

Badano, José L., Ansley, Stephen J., Leitch, Carmen C., Lewis, Richard Alan, Lupski, James R., Katsanis, Nicholas

Bardet-Biedl syndrome (BBS) is a genetically heterogeneous disorder, the primary features of which include obesity, retinal dystrophy, polydactyly, hypogenitalism, learning difficulties, and renal...

Genome Architecture Catalyzes Nonrecurrent Chromosomal Rearrangements

Stankiewicz, Paweł, Shaw, Christine J., Dapper, Jason D., Wakui, Keiko, Shaffer, Lisa G., Withers, Marjorie, ...

To investigate the potential involvement of genome architecture in nonrecurrent chromosome rearrangements, we analyzed the breakpoints of eight translocations and 18 unusual-sized deletions involving...

Genetic Interaction of BBS1 Mutations with Alleles at Other BBS Loci Can Result in Non-Mendelian Bardet-Biedl Syndrome

Beales, Philip L., Badano, Jose L., Ross, Alison J., Ansley, Stephen J., Hoskins, Bethan E., Kirsten, Brigitta, ...

Bardet-Biedl syndrome is a genetically and clinically heterogeneous disorder caused by mutations in at least seven loci (BBS1–7), five of which are cloned (BBS1, BBS2, BBS4, BBS6, and BBS7)....

Reciprocal Crossovers and a Positional Preference for Strand Exchange in Recombination Events Resulting in Deletion or Duplication of Chromosome 17p11.2

Bi, Weimin, Park, Sung-Sup, Shaw, Christine J., Withers, Marjorie A., Patel, Pragna I., Lupski, James R.

Smith-Magenis syndrome (SMS) is caused by an ∼4-Mb heterozygous interstitial deletion on chromosome 17p11.2 in ∼80%–90% of affected patients. Three large (∼200 kb), complex, and highly...

The Breakpoint Region of the Most Common Isochromosome, i(17q), in Human Neoplasia Is Characterized by a Complex Genomic Architecture with Large, Palindromic, Low-Copy Repeats

Barbouti, Aikaterini, Stankiewicz, Pawel, Nusbaum, Chad, Cuomo, Christina, Cook, April, Höglund, Mattias, ...

Although a great deal of information has accumulated regarding the mechanisms underlying constitutional DNA rearrangements associated with inherited disorders, virtually nothing is known about the...

Uncommon Deletions of the Smith-Magenis Syndrome Region Can Be Recurrent When Alternate Low-Copy Repeats Act as Homologous Recombination Substrates

Shaw, Christine J., Withers, Marjorie A., Lupski, James R.

Several homologous recombination “hotspots,” or sites of positional preference for strand exchanges, associated with recurrent deletions and duplications have been reported within large low-copy...

Position Effects Due to Chromosome Breakpoints that Map ∼900 Kb Upstream and ∼1.3 Mb Downstream of SOX9 in Two Patients with Campomelic Dysplasia

Velagaleti, Gopalrao V. N., Bien-Willner, Gabriel A., Northup, Jill K., Lockhart, Lillian H., Hawkins, Judy C., Jalal, Syed M., ...

Campomelic dysplasia (CD) is a semilethal skeletal malformation syndrome with or without XY sex reversal. In addition to the multiple mutations found within the sex-determining region Y–related...

Periaxin Mutations Cause Recessive Dejerine-Sottas Neuropathy

Boerkoel, Cornelius F., Takashima, Hiroshi, Stankiewicz, Pawel, Garcia, Carlos A., Leber, Steven M., Rhee-Morris, Laila, ...

The periaxin gene (PRX) encodes two PDZ-domain proteins, L- and S-periaxin, that are required for maintenance of peripheral nerve myelin. Prx−/− mice develop a severe demyelinating peripheral...