Another general rule is that-loss or gain of an autosome has more severe consequences than loss or gain of a sex chromosome. The most common sex chromosome abnormality is Monosomy of the X chromosome (45,X) or ‘Turner Syndrome. Another fairly common example is Klinefelter Syndrome (47,XXY). Although there is substantial variation within each syndrome, affected individuals often lead fairly normal lives. Occasionally an individual carries an extra chromosome which can't be identified by it's banding Pattern, these are called marker chromosomes. The introduction of FISH techniques has been a valuable tool in the identification of marker chromosomes. Structural abnormalities involve changes in the structure of one or more chromosomes. They can be incredibly complex but for the purposes of this discussion we will focus on the three of the more common types: 1. Deletions involve loss of material from a single chromosome. The effects are typically severe since there is a loss of genetic material. N . Inversions occur when there are two breaks within a single chromosome and the broken segment flips 180° (inverts) and reattaches to form a chromosome that is structurally out-of-sequence. There is usually no risk for problems to an individual if the inversion is of familial origin (has been inherited from a parent.) There is a slightly increased risk if it is a de novo (new) mutation due possibly to an interruption of a key gene sequence. Although an inversion carrier may be completely normal, they are at a slightly increased risk for producing a chromosomally unbalanced embryo. This is because an inverted chromosome has difficulty pairing with it's normal homolog during meiosis, which can result in gametes containing unbalanced derivative chromosomes if an unequal cross-over event occurs,3. Translocations involve exchange o fer between two or ‘chromosomes. If a translocation is reciprocal (balanced) the risk for problems to an individual is similar to that with inversions: usually none if familial and slightly increased if de novo. Problems arise with translocations when gametes from a balanced Parent are formed which do not contain both translocation products. When such a gamete combines with a normal gamete from the other Parent the result is an unbalanced embryo which is Partially monosomic for one chromosome and partially ‘risomic for the other. Numerical and structural abnormalities can be further divided into two main categories: constitutional, those you are born with; and acqui ired, those that arise as secondary changes to other diseases such as cancer. These are just some of the more common abnormalities encountered by a Cytogenetic Laboratory. Because the number of abnormal possibilities is almost infinite, a Cytogeneticist must be trained to detect and interpret virtually any chromosome abnormality that can occur, ‘nttp://home.comcast.net/~dmgt350/cytogenetics/geninfo htm, 112 ores Ler Gans s wrong This karyoty most comme characterize as: 47,XY,- + 47:1 + XY: * +21:: é Lf be \ rh Mgt AE ORE ae Re ae aa . tf 4 nae 3% 5» 8 i Figure 40: Karyotype of a person with Down Syndrome. ‘http://home, comcast This karyotype is an example of Down Syndrome (trisomy 21), the most commonnumerical abnormality found in newborns. It is characterized by an extra chromosome 21 and the karyotype is written as: 47,XY,+21. The key to the karyotype description is as follows: 47: the total number of chromosomes (46 is normal). « XY: the sex chromosomes (male). « +21: designates the extra chromosome as a 21. 1132. Inversion 10 % f Sy fh : ee nt ne ea + we WO re Jo ty a “ 4s 7 % “ eo i 3 Figure 41: Inversion 10 Karyotype. http://home.comcast.net/~dmgt350/cytogenetics/geninfo.htm This karyotype is an example of an inversion, one of the more common structural rearrangements. In this case a segment in the 4g, oF long arm of the right chromosome 10 is inverted. Since both breaks occurred in the long arm and the centromere is not involved, this is referred toas @ paracentric inversion. If separate breaks had occurred in both the long and short arms the centromere would be inverted as well, this would be} called a pericentric inversion. The karyotype is written as: 46,XY,inv(10)(q11.23q26.3). The key to the karyotype description is.as follows: + 46: the total number of chromosomes, , the sex chromosomes (male), + inv(10): inversion in chromosome 10, * (411.23q26.3): breakpoints of the inverted segment 14: | Inverted Chromosome 10 Figure 42: An elaboration of inversion. 3. Deletion 16 Karyotype ait23 j= 926.3 \ \ \ Normal Chromosome 10 3 18 ” 6 3 eer See 2 Figure 43: Deletion 16 karyotype. hittp://home. comcast. net/ ~dmgt350/cytogenetics/geninfo. htmau romosome. In “This karyotype isan example of a simple deletion one erromosome 16 this cose 9 opment within the g, or tong arm of the Ty visible is deleted, In sis particular example there are tWO PIETERS there had breaks within the long arm making it an interstitial oe enosome this been one break resulting in the loss of the end of a ‘ bir would be called a terminal deletion. The karyotype 'S description IS 2S as: 46,XX,del(16)(q13q22). The kev to the karvotype { follows: ? + 46: the total number of chromosomes. + XX: the sex (fame). a3 + del(46): deletion in i chromosome 16. a segment. Chromosome 16 - Chromosome 16 Figure 44: An elaboration of interstitial deletion. 4. Translocation (2;15) Karyotype MICK Wie Wawe Wl. Lé a+. as it be hd 8 a a + $4 “he oH } ® 45: Translocation (2;15) karyotype. Ww Inttp://home.comcast.net/ ~dmgt350/cytogenetics/geninfo.htm 116 Ais karyotype is an example of a balanced translocation between two chromosomes. In this case a large segment in the p, or short arm of the / right chromosome 2 has been exchanged with basically the entire g, or long arm of the right chromosome 15. Because the size of the exchanged ‘segments is about equal, this particular structural rearrangement would be almost impossible to detect without banding techniques. The karyotype is written as: 46,XY,t(2;15)(p11.2;q11.2). The key to the karyotype description is as follows: ¢ i + 46: the total number of chromosomes. + XY: the sex chromosomes (male). + (2;15): translocation between chromosomes 2 and 15. © (p11.2;q11.2): breakpoints in chromosomes 2 (p11.2), and 15 (q11.2) respectively. Jo ptt? Figure 46: An elaboration of translocation. u7 dit5. Translocation (5;8) Karyotype r Figure 47: ‘Translocation (5;8) Karyotype, hittp://home.comeast. nel/~dmgt350/ cytogenetics genio htm balanced translocation between two or lone a hanged with a small segnosn™ oF the . yotype is writtey #P23.1). The key to the karyotype dese tte” 46: the total number of chromosomes, = XY: the sex : chromosomes (male). a (5;8): translocation between chromosoines 5 Jas and 8. (q31.1;p23.1): breakpo ints in chromosomes 5 mermat Yamoewet nar Tamang (931.1), and 8 (p23.1) : Fig en Laboration , ure 48: An elaboration of thi respectively. translocation.6. Inversion 3 cell and ideogram aoe why aoe Normat 3 2 4 ° at . ee ys wt we Ss tha Inverted 337 e 8 « & Ped net geome Figure 49: Inversion 3 cell and ideogram. atpr//home. comcast net/~mgt350/evtogenetcs/ genio Him This metaphase cell is an example of a very subtle inversion. This is how the cell looks to a Cytogeneticist as it is viewed under a light microscope. In this case @ segment in the g, Or long arm of the indicated chromosome 3 is inverted: Since both breaks occurred in the long arm and the ‘centromere is not involved, this is referred to as aparacentric inversion. The karyotype is written a5: 46,XX,inv(3)(424q27). The key to the Karyotype description is as follows: «46: the total number of a a chromosomes. ¥ | Soe the sex chromosomes (female). : «= inv(3): Inversion in chromosome 3. slices © (q24q27):. breakpoints # i of the inverted segment. F Rea f Normal 3 he Figure 50: An elaboration of this Inversion, ifrae ear saga 4? a ssomeeccett arene deem, mae rm mt i fy ote ar Hoo Gg if hE. 42 ok feb HE is FE se ose j 3 Figure 51: Deletion 7 karyotype, http*//home. comcast.net ~cmgt350/cytogenetics/geninfo.htm This karyotype is an example of a simple deletion in one chromosome. In this case a segment within the g, Or long arm of the right chromosome 7 is deleted. In this particular example there are two microscopically visible breaks within the long arm making it a an interstitial deletion. If there had been | ‘one break resulting in the loss of the end of @ chromosome this would be called a terminal deletion. The karyotype is ‘ written as: 46,XY,del(7)(q11.23q21.2). my The key to the karyotype description is as follows: + 46: the total number of : chromosomes. ‘Normal Deleted * XY: the sex chromosomes (male), Chromosome 7 Chromosome 7 * del(7): deletion in chromosome 7. * (411.23q21.2): breakpoints of the _i9u"e 52: An elaboration of segment, this deletion, 120 |8. Dicentric (13314) Karyotype acon gts cS wecern Re tert Use Bt, teas peer Baw sex paw Figure 53: Dicentric (13;14) Karyotype. http://home.comcast.net/~dmgt350/cytogenetics/geninfo.htm “This karyotype is an example of a special type of translocation involving the entire long arms, and quite often the centromeres, of acrocentric chromosomes. It is called a Robertsonian Translocation. In this case the entire g, or long arm, plus centromere of a chromosome 13 has bes fused with the entire ¢ arm, plus centromere of a chromosome 14. The’ particular example is unbalanced and results in trisomy 13, There a is two normal chromosome 13's plus the chromosome 13 Involved wit translocation, thus there are three copies of chromosome 13, tht the translocation is shown as the right chromosome 14 in the kary. karyotype is written as:46,XY,+13,dic(13;14)(p11,2-p44 yetype. The to the karyotype description is as follows: 2). The key «46: the total number of chromosomes, The omosome Number remains 46 because the long arms of chromo: basically fused into one chromosome, somes 13 and 14 ree +» XY: the sex chromosomes (male), 121 ~~+13: indicates the presence of an extra chromosome 13. dic(13;; dicentric chromosome involving chromosomes 13 and 14. As with many Robertsonian translocations, the centromeres of both chromosomes are present, thus the "dicentric" designation. (p11.2;p11.2): breakpoints in chromosomes 13 (p11.2), and 14 (pi1.2) respectively. e o — pit? —pi12 Dicentric Chromosome 13 Chromosome 14 ‘Chromosome Figure 54; An elaboration of this translocation. 122 Read and analyze | option Which you t 1. What A von