Small supernumerary marker chromosome information

Small supernumerary marker chromosome (sSMC)
Other names	Small supernumerary chromosome
Representative karyotype from primary passage LX tumor cell 2. Karyotypic deviation: 57XX, +2, i(6)(p10), +7, +7, +8, +9, der(9)t(9 ;12)(p13 ;q11)ins(9;?)(p13;?), +11, +11, +12, +14, +15, +16, −17, del(17)(p11.2) , +21, −22, + mar.
Specialty	Medical genetics, pediatrics, oncology, gynecology, urology
Complications	Development of birth defects, infertility, neoplasms
Duration	lifetime
Causes	Abnormal de novo formation in a parent's gametes; direct inheritance from a parent carrying an intact sSMC
Prevention	Genetic counseling of carriers

A small supernumerary marker chromosome (sSMC) is an abnormal extra chromosome. It contains copies of parts of one or more normal chromosomes and like normal chromosomes is located in the cell's nucleus, is replicated and distributed into each daughter cell during cell division, and typically has genes which may be expressed. However, it may also be active in causing birth defects and neoplasms (e.g. tumors and cancers). The sSMC's small size makes it virtually undetectable using classical cytogenetic methods: the far larger DNA and gene content of the cell's normal chromosomes obscures those of the sSMC.^[1] Newer molecular techniques such as fluorescence in situ hybridization,^[2] next generation sequencing, comparative genomic hybridization,^[3] and highly specialized cytogenetic G banding analyses^[4] are required to study it. Using these methods, the DNA sequences and genes in sSMCs are identified and help define as well as explain any effect(s) it may have on individuals.^[5]

Human cells typically have 22 pairs of autosomal chromosomes and one pair of sex chromosomes. Each member of the paired autosomal chromosomes is identified as chromosome 1 up to 22; the pair of sex chromosomes are identified as the X and Y chromosomes with women's cells bearing two X chromosomes and men's cells bearing one X and one (male sex-determining) Y chromosome. sSMC are, by definition, smaller in size than one of the smaller human chromosomes, chromosome 20.^[6] They originate as copies of relatively small parts of one or more of the 46 chromosomes. Not all chromosomes are equally represented in sSMCs: ~65% of all sSMCs are copies of parts of chromosome 15 while only 7% are copies of parts of one of the five acrocentric chromosomes viz., chromosomes 13, 14, 15, 21, and 22.^[5] G banding analyses of sSMCs are commonly used to identify the chromosomes from which they were derived, the arms of these chromosomes ("p" for short arm, "q" for long arm) they contain, and the parts of these chromosomes' arms they have as defined by their G band contents. A sSMC containing part of chromosome 15's q arm between G bands 11.2 and 13.1 is described as 15q11.2–q13.1. sSMC's occur in ring or centric minute (linear with a central centromere) shapes, may contain inverted repeats of its genetic material, and may be an isochromosome. Isochromosomes have either two duplicate p or two duplicate q arms rather than the one p and one q arm of normal chromosomes. Thus, cells carrying a sSMC consisting of an isochromosome fragment have 2 extra copies of the genetic material in the sSMC and are termed tetrasomic. Cells carrying sSMCs that contain a non-duplicated fragment of a chromosome have one extra copy of the genetic material and are termed trisomic.^[5]

sSMCs' genes are clearly part of a cell's genotype, i.e. gene profile, but may not be activatable and therefore not alter an individual. In many cases, however, the genes in a sSMCs are active, over-expressed, and considered causes of the associated sSMC's disorder.^[7] sSMCs may form as a result of one or more of the following chromosomal events: incomplete trisomic rescue, chromothripsis-mediated partial trisomy rescue, U-type strand exchange, and/or rare types of genetic recombination. These events typically from an sSMC de novo during the meiosis divisions that form the sperm or egg cell or subsequently the zygote (i.e. fertilized egg) which develops into a fetus. Less commonly, however, parents may carry the sSMC and pass it to their descendants through their sperms or eggs. In either case, the sSMCs may acquire further changes in their genetic material at any time during development of the zygote or thereafter.^[8]

World-wide, small supernumerary marker chromosomes occur in ~4.2 per 10,000 individuals.^[5] Among sSMC-carrying individuals, ~70% acquired the sSMC as a result of a mutation(s) occurring during formation of their parent's sperm, egg, or zygoete while 30% inherited it directly from a parent carrying the intact sSMC (20% from a mother, 10% from a father). Rare cases of sSMCs' associated with neoplasms develop in individuals as a result of acquired mutations in their genome. Some 70% of individuals with a sSMC have no abnormalities and are unaware of it or learn of it by chance;^[7] the remaining ~30% acquire abnormalities during prenatal development that may be manifest in utero, at birth, or later in life. About 74% of acquired and >98% of inherited parentally transmitted sSMC-carrying individuals are developmentally normal.^[9] The sSMC-associated abnormalities include: mild to serious syndromes recognized congenitally (i.e. at birth) or in the fetus;^[5] infertility which is commonly detected in or near adulthood; and benign or malignant tumors that develop at virtually any age.^[10][11] There is a wide range of characteristics and traits among individuals with the same or similar sSMC. This is due to at least three mechanisms: 1) differences in the genomic contents of the sSMCs and/or individuals' genomes;^[12] 2) variable changes in the genetic material of sSMCs that develop over time;^[8] and 3) genetic mosaicism, i.e. variations in the distribution of the sSMC to different tissues and organs that occur during embryonic development or thereafter.^[7]