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Bernice E. Morrow - One of the best experts on this subject based on the ideXlab platform.
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retraction notice to nested inversion polymorphisms predispose chromosome 22q11 2 to meiotic rearrangements
American Journal of Human Genetics, 2018Co-Authors: Wolfram Demaerel, Matthew S. Hestand, Ann Swillen, Elfi Vergaelen, Elaine H Zackai, Marcos Lopezsanchez, Luis A Perezjurado, D M Mcdonaldmcginn, B Emanuel, Bernice E. MorrowAbstract:Inversion polymorphisms between low-copy repeats (LCRs) might predispose chromosomes to meiotic Non-Allelic Homologous Recombination (NAHR) events and thus lead to genomic disorders. However, for the 22q11.2 deletion syndrome (22q11.2DS), the most common genomic disorder, no such inversions have been uncovered as of yet. Using fiber-FISH, we demonstrate that parents transmitting the de novo 3 Mb LCR22A–D 22q11.2 deletion, the reciprocal duplication, and the smaller 1.5 Mb LCR22A–B 22q11.2 deletion carry inversions of LCR22B–D or LCR22C–D. Hence, the inversions predispose chromosome 22q11.2 to meiotic rearrangements and increase the individual risk for transmitting rearrangements. Interestingly, the inversions are nested or flanking rather than coinciding with the deletion or duplication sizes. This finding raises the possibility that inversions are a prerequisite not only for 22q11.2 rearrangements but also for all NAHR-mediated genomic disorders.
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dysregulation of tbx1 dosage in the anterior heart field results in congenital heart disease resembling the 22q11 2 duplication syndrome
Human Molecular Genetics, 2018Co-Authors: Erica Hasten, Bernice E. Morrow, Beverly S Emanuel, Elaine H Zackai, D M Mcdonaldmcginn, Terrence B Crowley, Silvia E RacedoAbstract:Non-Allelic Homologous Recombination events on chromosome 22q11.2 during meiosis can result in either the deletion (22q11.2DS) or duplication (22q11.2DupS) syndrome. Although the spectrum and frequency of congenital heart disease (CHD) are known for 22q11.2DS, there is less known for 22q11.2DupS. We now evaluated cardiac phenotypes in 235 subjects with 22q11.2DupS including 102 subjects we collected and 133 subjects that were previously reported as a confirmation and found 25% have CHD, mostly affecting the cardiac outflow tract (OFT). Previous studies have shown that global loss or gain of function (LOF; GOF) of mouse Tbx1, encoding a T-box transcription factor mapping to the region of synteny to 22q11.2, results in similar OFT defects. To further evaluate Tbx1 function in the progenitor cells forming the cardiac OFT, termed the anterior heart field, Tbx1 was overexpressed using the Mef2c-AHF-Cre driver (Tbx1 GOF). Here we found that all resulting conditional GOF embryos had a persistent truncus arteriosus (PTA), similar to what was previously reported for conditional Tbx1 LOF mutant embryos. To understand the basis for the PTA in the conditional GOF embryos, we found that proliferation in the Mef2c-AHF-Cre lineage cells before migrating to the heart, was reduced and critical genes were oppositely changed in this tissue in Tbx1 GOF embryos versus conditional LOF embryos. These results suggest that a major function of TBX1 in the AHF is to maintain the normal balance of expression of key cardiac developmental genes required to form the aorta and pulmonary trunk, which is disrupted in 22q11.2DS and 22q11.2DupS.
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nested inversion polymorphisms predispose chromosome 22q11 2 to meiotic rearrangements retracted
American Journal of Human Genetics, 2017Co-Authors: Wolfram Demaerel, Matthew S. Hestand, Ann Swillen, Elfi Vergaelen, Beverly S Emanuel, Elaine H Zackai, Marcos Lopezsanchez, Luis A Perezjurado, D M Mcdonaldmcginn, Bernice E. MorrowAbstract:Inversion polymorphisms between low-copy repeats (LCRs) might predispose chromosomes to meiotic Non-Allelic Homologous Recombination (NAHR) events and thus lead to genomic disorders. However, for the 22q11.2 deletion syndrome (22q11.2DS), the most common genomic disorder, no such inversions have been uncovered as of yet. Using fiber-FISH, we demonstrate that parents transmitting the de novo 3 Mb LCR22A–D 22q11.2 deletion, the reciprocal duplication, and the smaller 1.5 Mb LCR22A–B 22q11.2 deletion carry inversions of LCR22B–D or LCR22C–D. Hence, the inversions predispose chromosome 22q11.2 to meiotic rearrangements and increase the individual risk for transmitting rearrangements. Interestingly, the inversions are nested or flanking rather than coinciding with the deletion or duplication sizes. This finding raises the possibility that inversions are a prerequisite not only for 22q11.2 rearrangements but also for all NAHR-mediated genomic disorders.
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Nested Inversion Polymorphisms Predispose Chromosome 22q11.2 to Meiotic Rearrangements.
American journal of human genetics, 2017Co-Authors: Wolfram Demaerel, Matthew S. Hestand, Ann Swillen, Elfi Vergaelen, Beverly S Emanuel, Elaine H Zackai, Marcos López-sánchez, Luis A. Pérez-jurado, D M Mcdonald-mcginn, Bernice E. MorrowAbstract:Inversion polymorphisms between low-copy repeats (LCRs) might predispose chromosomes to meiotic Non-Allelic Homologous Recombination (NAHR) events and thus lead to genomic disorders. However, for the 22q11.2 deletion syndrome (22q11.2DS), the most common genomic disorder, no such inversions have been uncovered as of yet. Using fiber-FISH, we demonstrate that parents transmitting the de novo 3 Mb LCR22A–D 22q11.2 deletion, the reciprocal duplication, and the smaller 1.5 Mb LCR22A–B 22q11.2 deletion carry inversions of LCR22B–D or LCR22C–D. Hence, the inversions predispose chromosome 22q11.2 to meiotic rearrangements and increase the individual risk for transmitting rearrangements. Interestingly, the inversions are nested or flanking rather than coinciding with the deletion or duplication sizes. This finding raises the possibility that inversions are a prerequisite not only for 22q11.2 rearrangements but also for all NAHR-mediated genomic disorders.
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genetic dosage compensation in a family with velo cardio facial digeorge 22q11 2 deletion syndrome
American Journal of Medical Genetics Part A, 2011Co-Authors: Avishai A Alkalay, Tingwei Guo, Cristina Montagna, Cristina M Digilio, Bruno Dallapiccola, Bruno Marino, Bernice E. MorrowAbstract:Cytogenetic studies of a male child carrying the 22q11.2 deletion common in patients with velo-cardio-facial/DiGeorge syndrome showed an unexpected rearrangement of the 22q11.2 region in his normal appearing mother. The mother carried a 3 Mb deletion on one copy and a reciprocal, similar sized duplication on the other copy of chromosome 22q11.2 as shown by fluorescence in situ hybridization and array comparative genome hybridization analyses. The most parsimonious mechanism for the rearrangement is a mitotic Non-Allelic Homologous Recombination event in a cell in the early embryo soon after fertilization. The normal phenotype of the mother can be explained by the theory of genetic dosage compensation. This is the second documented case of such an event for this or any genomic disorder. This finding helps to reinforce this phenomenon in a human model, and has significant implications for recurrence risks for the dose-compensated mother.
Matthew S. Hestand - One of the best experts on this subject based on the ideXlab platform.
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retraction notice to nested inversion polymorphisms predispose chromosome 22q11 2 to meiotic rearrangements
American Journal of Human Genetics, 2018Co-Authors: Wolfram Demaerel, Matthew S. Hestand, Ann Swillen, Elfi Vergaelen, Elaine H Zackai, Marcos Lopezsanchez, Luis A Perezjurado, D M Mcdonaldmcginn, B Emanuel, Bernice E. MorrowAbstract:Inversion polymorphisms between low-copy repeats (LCRs) might predispose chromosomes to meiotic Non-Allelic Homologous Recombination (NAHR) events and thus lead to genomic disorders. However, for the 22q11.2 deletion syndrome (22q11.2DS), the most common genomic disorder, no such inversions have been uncovered as of yet. Using fiber-FISH, we demonstrate that parents transmitting the de novo 3 Mb LCR22A–D 22q11.2 deletion, the reciprocal duplication, and the smaller 1.5 Mb LCR22A–B 22q11.2 deletion carry inversions of LCR22B–D or LCR22C–D. Hence, the inversions predispose chromosome 22q11.2 to meiotic rearrangements and increase the individual risk for transmitting rearrangements. Interestingly, the inversions are nested or flanking rather than coinciding with the deletion or duplication sizes. This finding raises the possibility that inversions are a prerequisite not only for 22q11.2 rearrangements but also for all NAHR-mediated genomic disorders.
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nested inversion polymorphisms predispose chromosome 22q11 2 to meiotic rearrangements retracted
American Journal of Human Genetics, 2017Co-Authors: Wolfram Demaerel, Matthew S. Hestand, Ann Swillen, Elfi Vergaelen, Beverly S Emanuel, Elaine H Zackai, Marcos Lopezsanchez, Luis A Perezjurado, D M Mcdonaldmcginn, Bernice E. MorrowAbstract:Inversion polymorphisms between low-copy repeats (LCRs) might predispose chromosomes to meiotic Non-Allelic Homologous Recombination (NAHR) events and thus lead to genomic disorders. However, for the 22q11.2 deletion syndrome (22q11.2DS), the most common genomic disorder, no such inversions have been uncovered as of yet. Using fiber-FISH, we demonstrate that parents transmitting the de novo 3 Mb LCR22A–D 22q11.2 deletion, the reciprocal duplication, and the smaller 1.5 Mb LCR22A–B 22q11.2 deletion carry inversions of LCR22B–D or LCR22C–D. Hence, the inversions predispose chromosome 22q11.2 to meiotic rearrangements and increase the individual risk for transmitting rearrangements. Interestingly, the inversions are nested or flanking rather than coinciding with the deletion or duplication sizes. This finding raises the possibility that inversions are a prerequisite not only for 22q11.2 rearrangements but also for all NAHR-mediated genomic disorders.
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Nested Inversion Polymorphisms Predispose Chromosome 22q11.2 to Meiotic Rearrangements.
American journal of human genetics, 2017Co-Authors: Wolfram Demaerel, Matthew S. Hestand, Ann Swillen, Elfi Vergaelen, Beverly S Emanuel, Elaine H Zackai, Marcos López-sánchez, Luis A. Pérez-jurado, D M Mcdonald-mcginn, Bernice E. MorrowAbstract:Inversion polymorphisms between low-copy repeats (LCRs) might predispose chromosomes to meiotic Non-Allelic Homologous Recombination (NAHR) events and thus lead to genomic disorders. However, for the 22q11.2 deletion syndrome (22q11.2DS), the most common genomic disorder, no such inversions have been uncovered as of yet. Using fiber-FISH, we demonstrate that parents transmitting the de novo 3 Mb LCR22A–D 22q11.2 deletion, the reciprocal duplication, and the smaller 1.5 Mb LCR22A–B 22q11.2 deletion carry inversions of LCR22B–D or LCR22C–D. Hence, the inversions predispose chromosome 22q11.2 to meiotic rearrangements and increase the individual risk for transmitting rearrangements. Interestingly, the inversions are nested or flanking rather than coinciding with the deletion or duplication sizes. This finding raises the possibility that inversions are a prerequisite not only for 22q11.2 rearrangements but also for all NAHR-mediated genomic disorders.
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pseudoautosomal region 1 length polymorphism in the human population
PLOS Genetics, 2014Co-Authors: Martin A Mensah, Matthew S. Hestand, Maarten Larmuseau, Mala Isrie, Nancy Vanderheyden, Matthias Declercq, Erika Souche, Jeroen Van Houdt, Radka Stoeva, Hilde Van EschAbstract:The human sex chromosomes differ in sequence, except for the pseudoautosomal regions (PAR) at the terminus of the short and the long arms, denoted as PAR1 and PAR2. The boundary between PAR1 and the unique X and Y sequences was established during the divergence of the great apes. During a copy number variation screen, we noted a paternally inherited chromosome X duplication in 15 independent families. Subsequent genomic analysis demonstrated that an insertional translocation of X chromosomal sequence into theMa Y chromosome generates an extended PAR. The insertion is generated by Non-Allelic Homologous Recombination between a 548 bp LTR6B repeat within the Y chromosome PAR1 and a second LTR6B repeat located 105 kb from the PAR boundary on the X chromosome. The identification of the reciprocal deletion on the X chromosome in one family and the occurrence of the variant in different chromosome Y haplogroups demonstrate this is a recurrent genomic rearrangement in the human population. This finding represents a novel mechanism shaping sex chromosomal evolution.
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Pseudoautosomal region 1 length polymorphism in the human population.
Public Library of Science (PLoS), 2014Co-Authors: Martin A Mensah, Matthew S. Hestand, Maarten Larmuseau, Mala Isrie, Nancy Vanderheyden, Matthias Declercq, Erika Souche, Radka Stoeva, Jeroen Van Houdt, Hilde Van EschAbstract:The human sex chromosomes differ in sequence, except for the pseudoautosomal regions (PAR) at the terminus of the short and the long arms, denoted as PAR1 and PAR2. The boundary between PAR1 and the unique X and Y sequences was established during the divergence of the great apes. During a copy number variation screen, we noted a paternally inherited chromosome X duplication in 15 independent families. Subsequent genomic analysis demonstrated that an insertional translocation of X chromosomal sequence into the Y chromosome generates an extended PAR [corrected].The insertion is generated by Non-Allelic Homologous Recombination between a 548 bp LTR6B repeat within the Y chromosome PAR1 and a second LTR6B repeat located 105 kb from the PAR boundary on the X chromosome. The identification of the reciprocal deletion on the X chromosome in one family and the occurrence of the variant in different chromosome Y haplogroups demonstrate this is a recurrent genomic rearrangement in the human population. This finding represents a novel mechanism shaping sex chromosomal evolution
Wolfram Demaerel - One of the best experts on this subject based on the ideXlab platform.
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retraction notice to nested inversion polymorphisms predispose chromosome 22q11 2 to meiotic rearrangements
American Journal of Human Genetics, 2018Co-Authors: Wolfram Demaerel, Matthew S. Hestand, Ann Swillen, Elfi Vergaelen, Elaine H Zackai, Marcos Lopezsanchez, Luis A Perezjurado, D M Mcdonaldmcginn, B Emanuel, Bernice E. MorrowAbstract:Inversion polymorphisms between low-copy repeats (LCRs) might predispose chromosomes to meiotic Non-Allelic Homologous Recombination (NAHR) events and thus lead to genomic disorders. However, for the 22q11.2 deletion syndrome (22q11.2DS), the most common genomic disorder, no such inversions have been uncovered as of yet. Using fiber-FISH, we demonstrate that parents transmitting the de novo 3 Mb LCR22A–D 22q11.2 deletion, the reciprocal duplication, and the smaller 1.5 Mb LCR22A–B 22q11.2 deletion carry inversions of LCR22B–D or LCR22C–D. Hence, the inversions predispose chromosome 22q11.2 to meiotic rearrangements and increase the individual risk for transmitting rearrangements. Interestingly, the inversions are nested or flanking rather than coinciding with the deletion or duplication sizes. This finding raises the possibility that inversions are a prerequisite not only for 22q11.2 rearrangements but also for all NAHR-mediated genomic disorders.
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nested inversion polymorphisms predispose chromosome 22q11 2 to meiotic rearrangements retracted
American Journal of Human Genetics, 2017Co-Authors: Wolfram Demaerel, Matthew S. Hestand, Ann Swillen, Elfi Vergaelen, Beverly S Emanuel, Elaine H Zackai, Marcos Lopezsanchez, Luis A Perezjurado, D M Mcdonaldmcginn, Bernice E. MorrowAbstract:Inversion polymorphisms between low-copy repeats (LCRs) might predispose chromosomes to meiotic Non-Allelic Homologous Recombination (NAHR) events and thus lead to genomic disorders. However, for the 22q11.2 deletion syndrome (22q11.2DS), the most common genomic disorder, no such inversions have been uncovered as of yet. Using fiber-FISH, we demonstrate that parents transmitting the de novo 3 Mb LCR22A–D 22q11.2 deletion, the reciprocal duplication, and the smaller 1.5 Mb LCR22A–B 22q11.2 deletion carry inversions of LCR22B–D or LCR22C–D. Hence, the inversions predispose chromosome 22q11.2 to meiotic rearrangements and increase the individual risk for transmitting rearrangements. Interestingly, the inversions are nested or flanking rather than coinciding with the deletion or duplication sizes. This finding raises the possibility that inversions are a prerequisite not only for 22q11.2 rearrangements but also for all NAHR-mediated genomic disorders.
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Nested Inversion Polymorphisms Predispose Chromosome 22q11.2 to Meiotic Rearrangements.
American journal of human genetics, 2017Co-Authors: Wolfram Demaerel, Matthew S. Hestand, Ann Swillen, Elfi Vergaelen, Beverly S Emanuel, Elaine H Zackai, Marcos López-sánchez, Luis A. Pérez-jurado, D M Mcdonald-mcginn, Bernice E. MorrowAbstract:Inversion polymorphisms between low-copy repeats (LCRs) might predispose chromosomes to meiotic Non-Allelic Homologous Recombination (NAHR) events and thus lead to genomic disorders. However, for the 22q11.2 deletion syndrome (22q11.2DS), the most common genomic disorder, no such inversions have been uncovered as of yet. Using fiber-FISH, we demonstrate that parents transmitting the de novo 3 Mb LCR22A–D 22q11.2 deletion, the reciprocal duplication, and the smaller 1.5 Mb LCR22A–B 22q11.2 deletion carry inversions of LCR22B–D or LCR22C–D. Hence, the inversions predispose chromosome 22q11.2 to meiotic rearrangements and increase the individual risk for transmitting rearrangements. Interestingly, the inversions are nested or flanking rather than coinciding with the deletion or duplication sizes. This finding raises the possibility that inversions are a prerequisite not only for 22q11.2 rearrangements but also for all NAHR-mediated genomic disorders.
Elaine H Zackai - One of the best experts on this subject based on the ideXlab platform.
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retraction notice to nested inversion polymorphisms predispose chromosome 22q11 2 to meiotic rearrangements
American Journal of Human Genetics, 2018Co-Authors: Wolfram Demaerel, Matthew S. Hestand, Ann Swillen, Elfi Vergaelen, Elaine H Zackai, Marcos Lopezsanchez, Luis A Perezjurado, D M Mcdonaldmcginn, B Emanuel, Bernice E. MorrowAbstract:Inversion polymorphisms between low-copy repeats (LCRs) might predispose chromosomes to meiotic Non-Allelic Homologous Recombination (NAHR) events and thus lead to genomic disorders. However, for the 22q11.2 deletion syndrome (22q11.2DS), the most common genomic disorder, no such inversions have been uncovered as of yet. Using fiber-FISH, we demonstrate that parents transmitting the de novo 3 Mb LCR22A–D 22q11.2 deletion, the reciprocal duplication, and the smaller 1.5 Mb LCR22A–B 22q11.2 deletion carry inversions of LCR22B–D or LCR22C–D. Hence, the inversions predispose chromosome 22q11.2 to meiotic rearrangements and increase the individual risk for transmitting rearrangements. Interestingly, the inversions are nested or flanking rather than coinciding with the deletion or duplication sizes. This finding raises the possibility that inversions are a prerequisite not only for 22q11.2 rearrangements but also for all NAHR-mediated genomic disorders.
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dysregulation of tbx1 dosage in the anterior heart field results in congenital heart disease resembling the 22q11 2 duplication syndrome
Human Molecular Genetics, 2018Co-Authors: Erica Hasten, Bernice E. Morrow, Beverly S Emanuel, Elaine H Zackai, D M Mcdonaldmcginn, Terrence B Crowley, Silvia E RacedoAbstract:Non-Allelic Homologous Recombination events on chromosome 22q11.2 during meiosis can result in either the deletion (22q11.2DS) or duplication (22q11.2DupS) syndrome. Although the spectrum and frequency of congenital heart disease (CHD) are known for 22q11.2DS, there is less known for 22q11.2DupS. We now evaluated cardiac phenotypes in 235 subjects with 22q11.2DupS including 102 subjects we collected and 133 subjects that were previously reported as a confirmation and found 25% have CHD, mostly affecting the cardiac outflow tract (OFT). Previous studies have shown that global loss or gain of function (LOF; GOF) of mouse Tbx1, encoding a T-box transcription factor mapping to the region of synteny to 22q11.2, results in similar OFT defects. To further evaluate Tbx1 function in the progenitor cells forming the cardiac OFT, termed the anterior heart field, Tbx1 was overexpressed using the Mef2c-AHF-Cre driver (Tbx1 GOF). Here we found that all resulting conditional GOF embryos had a persistent truncus arteriosus (PTA), similar to what was previously reported for conditional Tbx1 LOF mutant embryos. To understand the basis for the PTA in the conditional GOF embryos, we found that proliferation in the Mef2c-AHF-Cre lineage cells before migrating to the heart, was reduced and critical genes were oppositely changed in this tissue in Tbx1 GOF embryos versus conditional LOF embryos. These results suggest that a major function of TBX1 in the AHF is to maintain the normal balance of expression of key cardiac developmental genes required to form the aorta and pulmonary trunk, which is disrupted in 22q11.2DS and 22q11.2DupS.
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nested inversion polymorphisms predispose chromosome 22q11 2 to meiotic rearrangements retracted
American Journal of Human Genetics, 2017Co-Authors: Wolfram Demaerel, Matthew S. Hestand, Ann Swillen, Elfi Vergaelen, Beverly S Emanuel, Elaine H Zackai, Marcos Lopezsanchez, Luis A Perezjurado, D M Mcdonaldmcginn, Bernice E. MorrowAbstract:Inversion polymorphisms between low-copy repeats (LCRs) might predispose chromosomes to meiotic Non-Allelic Homologous Recombination (NAHR) events and thus lead to genomic disorders. However, for the 22q11.2 deletion syndrome (22q11.2DS), the most common genomic disorder, no such inversions have been uncovered as of yet. Using fiber-FISH, we demonstrate that parents transmitting the de novo 3 Mb LCR22A–D 22q11.2 deletion, the reciprocal duplication, and the smaller 1.5 Mb LCR22A–B 22q11.2 deletion carry inversions of LCR22B–D or LCR22C–D. Hence, the inversions predispose chromosome 22q11.2 to meiotic rearrangements and increase the individual risk for transmitting rearrangements. Interestingly, the inversions are nested or flanking rather than coinciding with the deletion or duplication sizes. This finding raises the possibility that inversions are a prerequisite not only for 22q11.2 rearrangements but also for all NAHR-mediated genomic disorders.
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Nested Inversion Polymorphisms Predispose Chromosome 22q11.2 to Meiotic Rearrangements.
American journal of human genetics, 2017Co-Authors: Wolfram Demaerel, Matthew S. Hestand, Ann Swillen, Elfi Vergaelen, Beverly S Emanuel, Elaine H Zackai, Marcos López-sánchez, Luis A. Pérez-jurado, D M Mcdonald-mcginn, Bernice E. MorrowAbstract:Inversion polymorphisms between low-copy repeats (LCRs) might predispose chromosomes to meiotic Non-Allelic Homologous Recombination (NAHR) events and thus lead to genomic disorders. However, for the 22q11.2 deletion syndrome (22q11.2DS), the most common genomic disorder, no such inversions have been uncovered as of yet. Using fiber-FISH, we demonstrate that parents transmitting the de novo 3 Mb LCR22A–D 22q11.2 deletion, the reciprocal duplication, and the smaller 1.5 Mb LCR22A–B 22q11.2 deletion carry inversions of LCR22B–D or LCR22C–D. Hence, the inversions predispose chromosome 22q11.2 to meiotic rearrangements and increase the individual risk for transmitting rearrangements. Interestingly, the inversions are nested or flanking rather than coinciding with the deletion or duplication sizes. This finding raises the possibility that inversions are a prerequisite not only for 22q11.2 rearrangements but also for all NAHR-mediated genomic disorders.
Elfi Vergaelen - One of the best experts on this subject based on the ideXlab platform.
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retraction notice to nested inversion polymorphisms predispose chromosome 22q11 2 to meiotic rearrangements
American Journal of Human Genetics, 2018Co-Authors: Wolfram Demaerel, Matthew S. Hestand, Ann Swillen, Elfi Vergaelen, Elaine H Zackai, Marcos Lopezsanchez, Luis A Perezjurado, D M Mcdonaldmcginn, B Emanuel, Bernice E. MorrowAbstract:Inversion polymorphisms between low-copy repeats (LCRs) might predispose chromosomes to meiotic Non-Allelic Homologous Recombination (NAHR) events and thus lead to genomic disorders. However, for the 22q11.2 deletion syndrome (22q11.2DS), the most common genomic disorder, no such inversions have been uncovered as of yet. Using fiber-FISH, we demonstrate that parents transmitting the de novo 3 Mb LCR22A–D 22q11.2 deletion, the reciprocal duplication, and the smaller 1.5 Mb LCR22A–B 22q11.2 deletion carry inversions of LCR22B–D or LCR22C–D. Hence, the inversions predispose chromosome 22q11.2 to meiotic rearrangements and increase the individual risk for transmitting rearrangements. Interestingly, the inversions are nested or flanking rather than coinciding with the deletion or duplication sizes. This finding raises the possibility that inversions are a prerequisite not only for 22q11.2 rearrangements but also for all NAHR-mediated genomic disorders.
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nested inversion polymorphisms predispose chromosome 22q11 2 to meiotic rearrangements retracted
American Journal of Human Genetics, 2017Co-Authors: Wolfram Demaerel, Matthew S. Hestand, Ann Swillen, Elfi Vergaelen, Beverly S Emanuel, Elaine H Zackai, Marcos Lopezsanchez, Luis A Perezjurado, D M Mcdonaldmcginn, Bernice E. MorrowAbstract:Inversion polymorphisms between low-copy repeats (LCRs) might predispose chromosomes to meiotic Non-Allelic Homologous Recombination (NAHR) events and thus lead to genomic disorders. However, for the 22q11.2 deletion syndrome (22q11.2DS), the most common genomic disorder, no such inversions have been uncovered as of yet. Using fiber-FISH, we demonstrate that parents transmitting the de novo 3 Mb LCR22A–D 22q11.2 deletion, the reciprocal duplication, and the smaller 1.5 Mb LCR22A–B 22q11.2 deletion carry inversions of LCR22B–D or LCR22C–D. Hence, the inversions predispose chromosome 22q11.2 to meiotic rearrangements and increase the individual risk for transmitting rearrangements. Interestingly, the inversions are nested or flanking rather than coinciding with the deletion or duplication sizes. This finding raises the possibility that inversions are a prerequisite not only for 22q11.2 rearrangements but also for all NAHR-mediated genomic disorders.
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Nested Inversion Polymorphisms Predispose Chromosome 22q11.2 to Meiotic Rearrangements.
American journal of human genetics, 2017Co-Authors: Wolfram Demaerel, Matthew S. Hestand, Ann Swillen, Elfi Vergaelen, Beverly S Emanuel, Elaine H Zackai, Marcos López-sánchez, Luis A. Pérez-jurado, D M Mcdonald-mcginn, Bernice E. MorrowAbstract:Inversion polymorphisms between low-copy repeats (LCRs) might predispose chromosomes to meiotic Non-Allelic Homologous Recombination (NAHR) events and thus lead to genomic disorders. However, for the 22q11.2 deletion syndrome (22q11.2DS), the most common genomic disorder, no such inversions have been uncovered as of yet. Using fiber-FISH, we demonstrate that parents transmitting the de novo 3 Mb LCR22A–D 22q11.2 deletion, the reciprocal duplication, and the smaller 1.5 Mb LCR22A–B 22q11.2 deletion carry inversions of LCR22B–D or LCR22C–D. Hence, the inversions predispose chromosome 22q11.2 to meiotic rearrangements and increase the individual risk for transmitting rearrangements. Interestingly, the inversions are nested or flanking rather than coinciding with the deletion or duplication sizes. This finding raises the possibility that inversions are a prerequisite not only for 22q11.2 rearrangements but also for all NAHR-mediated genomic disorders.