Rinčić Martina, Iourov Ivan Y, Liehr Thomas
Croatian Institute for Brain Research, School of Medicine University of Zagreb, Salata 12, 10000 Zagreb, Croatia.
Mental Health Research Center, Moscow, 117152 Russia ; Ministry of Health of Russian Federation, Separated Structural Unit "Clinical Research Institute of Pediatrics" at Pirogov Russian National Research Medical University, Moscow, 125412 Russia ; Moscow State University of Psychology and Education, Moscow, 127051 Russia.
Mol Cytogenet. 2016 Aug 8;9:56. doi: 10.1186/s13039-016-0271-7. eCollection 2016.
Chromosome counting is a process in which cells determine somehow their intrinsic chromosome number(s). The best-studied cellular mechanism that involves chromosome counting is 'chromosome-kissing' and X-chromosome inactivation (XCI) mechanism. It is necessary for the well-known dosage compensation between the genders in mammals to balance the number of active X-chromosomes (Xa) with regard to diploid set of autosomes. At the onset of XCI, two X-chromosomes are coming in close proximity and pair physically by a specific segment denominated X-pairing region (Xpr) that involves the SLC16A2 gene.
An Ensembl BLAST search for human and mouse SLC16A2/Slc16a2 homologues revealed, that highly similar sequences can be found at almost each chromosome in the corresponding genomes. Additionally, a BLAST search for SLC16A2/TSIX/XIST (genes responsible for XCI) reveled that "SLC16A2/TSIX/XIST like sequences" cover equally all chromosomes, too. With respect to this we provide following hypotheses.
If a single genomic region containing the SLC16A2 gene on X-chromosome is responsible for maintaining "balanced" active copy numbers, it is possible that similar sequences or gene/s have the same function on other chromosomes (autosomes). SLC16A2 like sequences on autosomes could encompass evolutionary older, but functionally active key regions for chromosome counting in early embryogenesis. Also SLC16A2 like sequence on autosomes could be involved in inappropriate chromosomes pairing and, thereby be involved in aneuploidy formation during embryogenesis and cancer development. Also, "SLC16A2/TSIX/XIST gene like sequence combinations" covering the whole genome, could be important for the determination of X:autosome ratio in cells and chromosome counting.
SLC16A2 and/or SLC16A2/TSIX/XIST like sequence dispersed across autosomes and X-chromosome(s) could serve as bases for a counting mechanism to determine X:autosome ratio and could potentially be a mechanism by which a cell also counts its autosomes. It could also be that such specific genomic regions have the same function for each specific autosome. As errors during the obviously existing process of chromosome counting are one if not the major origin of germline/somatic aneuploidy the here presented hypotheses should further elaborated and experimentally tested.
染色体计数是细胞以某种方式确定其固有染色体数目的过程。研究最为充分的涉及染色体计数的细胞机制是“染色体亲吻”和X染色体失活（XCI）机制。对于哺乳动物中众所周知的性别间剂量补偿而言，平衡活性X染色体（Xa）的数量与常染色体的二倍体组是必要的。在XCI开始时，两条X染色体紧密靠近，并通过一个涉及SLC16A2基因的特定片段（称为X配对区域，Xpr）进行物理配对。
对人类和小鼠SLC16A2/Slc16a2同源物进行的Ensembl BLAST搜索显示，在相应基因组的几乎每条染色体上都能找到高度相似的序列。此外，对SLC16A2/TSIX/XIST（负责XCI的基因）进行的BLAST搜索表明，“SLC16A2/TSIX/XIST样序列”也同样覆盖了所有染色体。基于此，我们提出以下假设。
如果X染色体上单个包含SLC16A2基因的基因组区域负责维持“平衡”的活性拷贝数，那么其他染色体（常染色体）上的相似序列或基因可能具有相同功能。常染色体上的SLC16A2样序列可能包含在早期胚胎发育中用于染色体计数的进化上更古老但功能活跃的关键区域。此外，常染色体上的SLC16A2样序列可能参与不适当的染色体配对，从而在胚胎发育和癌症发展过程中参与非整倍体的形成。而且，覆盖整个基因组的“SLC16A2/TSIX/XIST基因样序列组合”可能对细胞中X:常染色体比例的确定和染色体计数很重要。
分散在常染色体和X染色体上的SLC16A2和/或SLC16A2/TSIX/XIST样序列可能作为一种计数机制的基础，用于确定X:常染色体比例，并且可能是细胞对其常染色体进行计数的一种机制。也有可能这样的特定基因组区域对每个特定常染色体具有相同功能。由于在明显存在的染色体计数过程中的错误是生殖系/体细胞非整倍体的一个（如果不是主要的）起源，因此本文提出的假设应进一步阐述并进行实验验证。
