title: Genetic dosage and position effect of small supernumerary marker chromosome (sSMC) in human sperm nuclei in infertile male patient.
abstract: Chromosomes occupy specific distinct areas in the nucleus of the sperm cell that may be altered in males with disrupted spermatogenesis. Here, we present alterations in the positioning of the human chromosomes 15, 18, X and Y between spermatozoa with the small supernumerary marker chromosome (sSMC; sSMC(+)) and spermatozoa with normal chromosome complement (sSMC(-)), for the first time described in the same ejaculate of an infertile, phenotypically normal male patient. Using classical and confocal fluorescent microscopy, the nuclear colocalization of chromosomes 15 and sSMC was analyzed. The molecular cytogenetic characteristics of sSMC delineated the karyotype as 47,XY,+der(15)(pter->p11.2::q11.1->q11.2::p11.2->pter)mat. Analysis of meiotic segregation showed a 1:1 ratio of sSMC(+) to sSMC(-) spermatozoa, while evaluation of sperm aneuploidy status indicated an increased level of chromosome 13, 18, 21 and 22 disomy, up to 7 × (2.7 - 15.1). Sperm chromatin integrity assessment did not reveal any increase in deprotamination in the patient's sperm chromatin. Importantly, we found significant repositioning of chromosomes X and Y towards the nuclear periphery, where both chromosomes were localized in close proximity to the sSMC. This suggests the possible influence of sSMC/XY colocalization on meiotic chromosome division, resulting in abnormal chromosome segregation, and leading to male infertility in the patient.
authors.affiliation: Institute of Human Genetics, Polish Academy of Sciences, Department of Reproductive Biology and Stem Cells, Strzeszynska 32, 60-479 Poznan, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Olszewska
authors.affiliation: Institute of Human Genetics, Polish Academy of Sciences, Department of Reproductive Biology and Stem Cells, Strzeszynska 32, 60-479 Poznan, Poland.
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Wanowska
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh 15213, PA, USA.
authors.forename: Archana
authors.initials: A
authors.lastname: Kishore
authors.affiliation: Institute of Hereditary Pathology, Ukrainian Academy of Medical Sciences, Lysenko Str. 31a, 79000 Lviv, Ukraine.
authors.forename: Nataliya
authors.initials: N
authors.lastname: Huleyuk
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh 15213, PA, USA.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Georgiadis
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh 15213, PA, USA.
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Yatsenko
authors.affiliation: Institute of Hereditary Pathology, Ukrainian Academy of Medical Sciences, Lysenko Str. 31a, 79000 Lviv, Ukraine.
authors.forename: Mariya
authors.initials: M
authors.lastname: Mikula
authors.affiliation: Institute of Hereditary Pathology, Ukrainian Academy of Medical Sciences, Lysenko Str. 31a, 79000 Lviv, Ukraine.
authors.forename: Danuta
authors.initials: D
authors.lastname: Zastavna
authors.affiliation: Institute of Human Genetics, Polish Academy of Sciences, Department of Reproductive Biology and Stem Cells, Strzeszynska 32, 60-479 Poznan, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Wiland
authors.affiliation: Institute of Human Genetics, Polish Academy of Sciences, Department of Reproductive Biology and Stem Cells, Strzeszynska 32, 60-479 Poznan, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Kurpisz
mesh_terms: D000328:Adult; D000782:Aneuploidy; D002467:Cell Nucleus; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D020090:Chromosome Segregation; D018628:Gene Dosage; D005819:Genetic Markers; D006579:Heterozygote; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007248:Infertility, Male / Q000235:genetics*; D007621:Karyotyping; D008297:Male; D008540:Meiosis / Q000235:genetics; D013094:Spermatozoa / Q000378:metabolism*
chemical_list: D002843:Chromatin; D005819:Genetic Markers