2658-6533Research Results in Biomedicine2658-653310.18413/2313-8955-2019-5-1-0-21606GeneticsFirst report on a 20qh+ heteromorphism characterized by molecular cytogenetics as amplification of D20Z1 sequencesFirst report on a 20qh+ heteromorphism characterized by molecular cytogenetics as amplification of D20Z1 sequencesPadutschNiklasPadutschNiklasLiehr@med.uni-jena.deLiehrThomasLiehrThomasThomas.Liehr@med.uni-jena.de20195100

Background: Chromosomal heteromorphisms (CHMs) in human are still understudied. This is partially due to the fact that heterochromatic regions are not well documented in human genome browsers, even though data would be available. Another peculiarity associated with CHMs is that they are routinely seen in cytogenetic analyses, however, considered as being without any clinical meaning. Nonetheless, CHMs are more frequently observed in infertility patients, suggesting very well a potential impact for human genome function. Aim of the study: Since literature is still lacking the exact characterization or complete documentation of numerous CHMs, we aimed to characterize CHMs on chromosome 20 and to characterize whether these result from an amplification of D20Z1 or D20Z2 or both. Materials and methods: An infertile adult and a fetus have been studied by fluorescence in situ hybridization (FISH) with D20Z2 (specific for 20p11.1) and D20Z1 (specific for 20q11.1) probes. Results: Here we prove for the first time that the two different types of CHMs in chromosome 20 are indeed caused by amplification of two different stretches of the alphoid DNA: 20ph+ variants are normally due to enlarged D20Z2-stretches while 20qh+ variants are caused by enlargement of D20Z1-stretches. Conclusions: We have characterized 20qh+ CHM by means of FISH for the first time showing it to result from amplification of D20Z1. This is another puzzle piece for exact characterization and complete documentation of CHMs in human.

Background: Chromosomal heteromorphisms (CHMs) in human are still understudied. This is partially due to the fact that heterochromatic regions are not well documented in human genome browsers, even though data would be available. Another peculiarity associated with CHMs is that they are routinely seen in cytogenetic analyses, however, considered as being without any clinical meaning. Nonetheless, CHMs are more frequently observed in infertility patients, suggesting very well a potential impact for human genome function. Aim of the study: Since literature is still lacking the exact characterization or complete documentation of numerous CHMs, we aimed to characterize CHMs on chromosome 20 and to characterize whether these result from an amplification of D20Z1 or D20Z2 or both. Materials and methods: An infertile adult and a fetus have been studied by fluorescence in situ hybridization (FISH) with D20Z2 (specific for 20p11.1) and D20Z1 (specific for 20q11.1) probes. Results: Here we prove for the first time that the two different types of CHMs in chromosome 20 are indeed caused by amplification of two different stretches of the alphoid DNA: 20ph+ variants are normally due to enlarged D20Z2-stretches while 20qh+ variants are caused by enlargement of D20Z1-stretches. Conclusions: We have characterized 20qh+ CHM by means of FISH for the first time showing it to result from amplification of D20Z1. This is another puzzle piece for exact characterization and complete documentation of CHMs in human.

D20Z1D20Z220ph+20qh+chromosomal heteromorphisms (CHMs)humanD20Z1D20Z220ph+20qh+chromosomal heteromorphisms (CHMs)human

The clinical cases were provided by Dr. A. Ovens-Reader Munich, Germany and Dr. I. Bartels, Germany.

Список литературыLiehr T. Benign & Pathological Chromosomal Imbalances, Microscopic and Submicroscopic Copy Number Variations (CNVs) in Genetics and Counseling. 1st ed. New York: Academic Press; 2014.Liehr T. 201X. Cases with Heteromorphisms. [Internet].  [cited 2018 Dec 12]. Available from: http://ssmc-tl.com/HMs.htmlRocchi M, Baldini A, Archidiacono N, et al. Chromosome-specific subsets of human alphoid DNA identified by a chromosome 2-derived clone. Genomics. 1990;8(4):705-709. DOI: https://doi.org/10.1016/0888-7543(90)90258-VBassi C, Magnani I, Sacchi N, et al. Molecular structure and evolution of DNA sequences located at the alpha satellite boundary of chromosome 20. Gene. 2000;256(1-2):43-50. DOI: https://doi.org/10.1016/S0378-1119(00)00354-1Weise A, Liehr T. Pre- and postnatal diagnostics and research on peripheral blood, bone marrow chorion, amniocytes, and fibroblasts. In: Fluorescence in situ Hybridization (FISH) – Application Guide, T Liehr (ed.), 2nd e. Berlin: Springer; 2017:171-180.Kosyakova N, Weise A, Mrasek K, et al. The hierarchically organized splitting of chromosomal bands for all human chromosomes. Mol Cytogenet. 2009;2:4. DOI: 10.1186/1755-8166-2-4Liehr T, editor. Fluorescence in situ Hybridization (FISH) – Application Guide, 2nd ed. Berlin: Springer; 2017.Kosyakova N, Grigorian A, Liehr T, et al. Heteromorphic variants of chromosome 9. Mol Cytogenet. 2013;6(1):14. DOI: 10.1186/1755-8166-6-14Girirajan S, Rosenfeld JA, Cooper GM, et al. A recurrent 16p12.1 microdeletion supports a two-hit model for severe developmental delay. Nat Genet. 2010;42(3):203-209. DOI: 10.1038/ng.534Liehr T. Benign and pathological gain or loss of genetic material- about microscopic and submicroscopic copy number variations (CNVs) in human genetics. Tsitologiia. 2016;58(6):476-477.