Babak Nami
1. Introduction The discovery of the chromosomal etiology of any abnormalities likes Down syndrome, Turner syndrome, Klinefelter syndrome, etc was irregular to classify and give an account them. The need for guidelines and standardization of terminology thus become imperative, therefore hold some international conf confer eren ence ces s on huma human n chro chromo moso some me nome nomenc ncla latu ture re:
2. Human chromosomes •
There is 46 chromosomes in a normal human somatic cell. Of them 44 are autosomes and and 2 are are sex sex chro chromo moso some mes. s.
•
The autosomes are assigned in descending order of length, size and centromere posi positi tion on of each each pair pair.. Sex Sex chro chromo moso some mess assi assign gn at last last..
•
In a normal male the sex chromosomes are XY, and in a normal female ,th ,they are XX.
• According to Chicago Chicago conference conference chromosomes in the centromere centromere position classified into three basic categories:
Metacentric: a chromosome whit its centromere placed in middle Sub-metacentric : a chromosome whit its centromere placed closer to one end of it Acrocentric : a chromosome whit its centromere placed almost one end of it
3. Chromosomes Identification Identification of individual chromosomes and chromosome regions for extracted chromosomes at metaphase late become possible with banding techniques:
3.1. G-banding : there is refers to staining by Giemsa after digesting the chromosomes chromosomes with trypsin. In this pattern dark bands in a light background are available. This method will normally produce 300-400 bands in a normal, human genome and is using routinely in USA, Canada and many countries. countries. 3.2. Q-banding : utilize quinacrine mustard or similar matters and fluorescence . in G-banding pattern. 3.3. R-banding: is the reverse of G-banding (the R stands for "reverse"). The dark regions are euchromatic (guanine-cytosine rich regions) and the bright regions are heterochromatic (thymine-adenine rich regions).This method is useful to observe bands that don’t sufficiently stained stained in G and Q banding. R-banding is a standard method for distinguish any chromosome abnormality at the European countries like France especially. 3.4. C-banding : Staining centromeric region and ‘ Constitutive heterochromatin’ is basis matter in this method.
G-banding pattern
Q-ba Q-band ndin in
att attern ern
Normal 46,XY male karyotype. Characteris Characteristic tic G-banding (top) and fluorescent fluorescent Q-banding (bottom). (bottom). The same cell was used for both methodologies to demonstrate the complementary banding patterns.
4. Chromosomes Description 4.1. Chromosomes Arms: Each chromosome divided by the centromere into a short or ‘p’ arm (from the French petit) and a long or ‘q’ arm (from the French queue). Region from centromere to end of p arm called “p10”, “p10”, and from the centromere to end of q arm called “q10”:
4.2. Chromosomes regions : Each chromosome arm is divided into regions. This division is based on certain landmarks present on each chromosomes. A region is an area that lies between two landmarks. The two regions immediately adjacent to the centromere are designated as “1” (p1 and q1), the next distal as “2”, and so on. 4.3. Chromosomes bands and subbands : Regions are divided into bands and the bands into subbands. A band is that part of a chromosome that is distincly different from the adjacent area by virtue of being lighter or darker in staining intensity. • Each band defined as a numbered and after a related region number. • su an e ne as a num er a er a o s gn g n a po po n e a er re a e an number Example: The terminal band in the long arm of chromosome 2 can be written as :
2q37 To mean chromosome 2, long arm, region 3, band 7 and is referred to as
“ Two q Three Seven” not
“Two q Thirty-seven”
2q24.3 Chromosome: 2 Arm:
Long(q)
Region:
2
Band:
4
5. Karyotyp Karyotypee Descripti Descriptions ons 1. A normal female karyotype is written as 46,XX and normal male karyotype as 46,XY Note:: the characters are contiguous, Note contiguous, without space between items. 2. Sex chromosome abnormalities abnormalit ies are describe first, following by autosomal changes in numerical order. For each chromosome described, numerical changes are listed before structural abnormalities.
6. Nomenclature of chromosomes abnormalities There are two groups of abnormalities discussed about chromosomes:
6.1. Numerical abnormalities of chromosomes chromosomes : The term “numerical abnormalities” refers to changes in the number of chr chromo omosom somes by gain gain or loss loss of chr chromo omosom some(s). s). This This is calle alled d Aneoplo oploid idy y too too (an abnormal number of chromosomes), and occurs when an individual is missing either a chromosome from a pair (monosomy) or has more than two chromo chromosom somes es of a pair pair (Tris (Trisomy omy,, Tetraso etrasomy my,, etc). etc).
6.2. Structural chromosome abnormalities: • • • • • •
When the chromosome's structure is altered. This can take several forms: Deletions Duplications Translocations Inversions Rings Isochromosomes
Aneoploidie Aneoploidiess involving involving the sex sex chromosomes chromosomes • Constitutional : (5% of whole pregnancies) 45,X
Classical monosomy monosomy X or Turner Turner syndrome syndrome
47,XXY 47,XXX 48,XXYY
Classical Klinefelter Klinefelter syndrome syndrome A female with three X chromosomes Variant of klinefelter klinefelter syndrome syndrome
• Acquired : (Certain leukemias leukemias and solid tumors) 45,X,-X (Normal female with two X chromosomes but with the loss of one X in her tumor cells )
47,XX,+X (Normal female with two X chromosomes and gain of an extra X in her tumor cells)
48,XY,+X,+Y (This is describes a male with acquired X and Y chromosomes his tumor)
48,XXYc,+X syndrome who has an acquired X chromosome in his (Here, we have a patient with klinefelter syndrome tumor cells. The letter “c” is placed next to XXY to show that the patient’s sex chromosome complement is XXY and not XY or XXXX )
Numerical Abnormalities Abnormalities of the Autosomes
In this matter the exception that (+) and (-) signs are used to designate constitutionals.
47,XY,+18
Male Male with with trisom trisomy y 18
48,XX,+18+21 Female Female with both both trisom trisomy y 18 and and trisom trisomy y 21 45,XY,-21 Male with monosom monosomy y 21 46,XY,+21c,-21 Male trisomy trisomy 21 patient patient with loss of one one chromosome 21 in his tumor cells 48,XX,+21c,+21 Female with trisomy trisomy 21 and gain gain of an additional chromosome 21 an her tumor cells
Mosaics and Chimeras An individual with two or more cell types, differing in chromosome number or structure is either a mosaic or a chimera.
Mosaic: the cell types originated from a single zygote. zygote that Chimera: the cell types originated from two or more zygote subsequently fused.
• In designating mosaic or chimera karyotype, a slash (/) is used to separate separate the cell lines. • The actual number of cells detected in each clone can be given within [ ]. • The largest clone is recorded first, then the next largest, and so on. • Whenever a normal cell line is present, it is always recorded last, irrespective of the number of normal cells detected .
mos 45,X[4]/46,XX[16]
This is Turner mosaic with tw two o ce cell ll li line ness.
mos 45,X 45,X[[4]/46,XX ]/46,XX[[16 16]] Analysis of 20 cells (4+16) showed that this individual has 4 cells that are 45,X and 16 cells are 46,XX 46,XX..
Mos 45,X[5]/47,XYY[5]/46,XY[10] This represents a mosaic with three cell lines. In a chimera where the two cell lines are normal (46,XX and 46,XY) and both are present in equal proportions, either one of them can be listed first. If one cell line is larger clone is listed first. chi 46,XX[10]/46,XY[10] This describes a chimera with female and male cells in equal number. number. chi 47,XX+21[15]/46,XY[5] This is a chimera with both female and male cell lines. The female cell line shows trisomy 21, whereas the male cell line is normal. chi 69,XXX[20]/46,XY[5] This represents a chimera with triploud and diploid cell lines. The triploid line is XXX, whereas the diploid line is XY. Note: Use of the abbreviations “chi” and “mos” is optional, as the presence of Note: chimerism or mosaicism is usually evident from the karyotype.
Structural chromosome abnormalities These abnormalities are less common in comparison with aneoploidy, accurse in 1 case of 375 alive births.
chromosome number in parentheses [e.g. r(X), del(2), ins(4), • Involved chromosome dup(5)].
• If two or more chromosomes are involved in a rearrangement, as with translocation, translocation, a semicolon (;) is used to separate chromosome numbers within paren eses e.g. ; , ; ; .
• Chromosome are listed in numerical order unless a sex chromosome is involved involved [e.g. t(X;1) or t(Y;15)]. t(Y;15)].
• If in the same cell, a specific chromosome is involved in both a numerical and a structural rearrangement, the numerical abnormality is designated first [e.g. +13,t(13;14)].
Additional Material, Origin Unknown (add)
When a chromosome has additional material attached to it, the origin of this material might not be identifiable with conventional banding methods. To represent the abbreviation “add” (from the Latin additio) is used.
46 XX add 17 13 Additional material of unknown origin is attached to chromosome 17 at band p13 46,XX,add(9)(q22) Additional material of unknown origin attached to chromosome 9 at q22
Deletions (del) This is an aberration in which a part of a chromosome is lost. Deletions can be either terminal, where all chromosomal material from the breakpoint on is lost, or interstitial, in which an interstitial section of one arm is missing .
• Terminal Deletions 46,XY,del,(1)(q32) 46,XY,del(1)(pter
(short form)
q32)
(long form)
This karyotype describes a terminal deletion deletion involving the long arm of chromosome chromosome 1, the colon present in the long form indicates a break at band 1q32 and deletion of the region distal distal to it. The rest of the chromosome, chromosome, from 1 pter to 1q32, is present.
• Interstitial Deletions 46,XY,del(1)(p21p32) 46,X 46,XY Y,de ,del(1) l(1)(p (pte terr
p21: p21::p :p3 32
(short form) qte qter) r) (long form)
Breakage and reunion are represented in the long form by double colon (::). Here, this occurred involving bands 1q21 and 1p32 segment between them has been deleted.
Derivative Chromosomes (der) A structurally rearranged chromosome generated by events involving two or more chromosomes chromosomes or the result of multiple events within a single chromosome is a derivative chromosome. Thus, each unbalanced product of a translocation event is a derivative chromosome. The identify of a derivative chromosome is determined by its centromere.
46,XY,der(3)t(3;6)(p21;q23) The derivative derivative chromosome 3 in this karyotype karyotype is the result of a translocation between between the short arm of chromosome 3 at band p21 and the long arm of chromosome 6 at band q23. The der(3) replaces one normal chromosome 3, and both chromosomes 6 are normal. This unbalanc unbalanced ed karyotype karyotype results results in monosom monosomy y (loss) (loss) of region region 3p21 pter and trisomy (gain) of 6q23 pter. pter. This karyotype is the product of adjacent-1 segregation. segregation. 45,XY,der(3)t(3;6)(p21;q23),-6 the der(3) is same as in the above example and again replaces one of the normal chromosomes 3. However, there is only one normal chromosome 6 in the case, resulting in monosomy for both 3p21 pter and 6pter q23. This is the result of 3:1 segregation.
Recombinant Chromosomes (rec) Recombinant chromosomes are also structurally rearranged chromosomes. They arise de novo from meiotic crossing-over between homologous chromosomes when one is structurally abnormal .
46,XY,rec(3)dup(3p)inv(3)(p21q27) 46,XY,rec(3)dup(3p)inv(3)(p21q27) One normal chromosome 3 has been replaced by a recombinant chromosome 3. The segment 3q21 pter is duplicated, duplicated, and the segment from 3q27 qter is deleted. The key to interpreting interpreting this karyotype is “dup(3p)”; “dup(3p)”; dup indicates a duplication.
Fragile Sites (fra) A male would be described as 46,Y,fra(X)(q27.3), 46,Y,fra(X)(q27.3), and a female would be 46,X,fra(X)(q27.3). Other fragile sites are described in the same way for example: 46,XY,fra(12)(q13.1)
Insertions (ins) An insertion is a structural structural rearrangement in which a part of a chromosome is typically insertitially repositioned into a differen differentt area of the karyorype. Insertion can occur within a chromosome or between two chromosomes.
• Insertion Within a Chromosome 46,XX,ins(3)(p21q27q32) This represents a direct insertion. The long arm segment between bands 3q32 has broken away and been inserted into the short arm of the same chromosome at band p21. NOTE: the orientation orientation of the inverted segment has no changed (i.e., band q27 is still proximal proximal to the centromer centromer relative to to band q32)
• Insertion Between Two Chromosomes 46,XX,ins(4;9)(q31;q12q13) The long arm segment between bands 9q12 and 9q13 has been inserted, in its original orientation, into the long arm of chromosome 4 at band q31.
Inversions (inv) A chromosomal aberration in which a segment of a chromosome is reversed in orientation but not relocated is called an inversion. • Paracentric Inversions: Involve only one arm of a chromosome. • Precentric Inversions: Involve both arms of a chromosome and therefore, include the centromere. xamp es:
46,XY,inv(3)(p21q31) Break and reunion occurred at band q21 and q27 in long arm of chromosome 3. The segment lying between these breakpoints has been reattached with its bands in reverse (inverted) order.
46.XY,inv(2)(p21q31) Break and reunion occurred at bands p21 (short (short arm) arm) and q31 (long (long arm) arm) of chromosome 2. The segment between these bans, including the centromere, was reattached with its bands in inverted order
Isochr Isochromo omosom somes es (i) An abnormal chromosome in which one arm is duplicated The breakpoint in an isochromosome is assigned to the centromer, at band p10 or q10, depending on which arm is duplicated:
46,XX,i(18)(p10) This describes an isochromosome for the short arm of chromosome 18, as evident by assigning the breakpoint to band p10.
46,XX,i(18)(q10) This describes an isochromosome for the long arm of a chromosome 18; the creakpoint is assigned to q10.
Isodicentri Isodicentricc Chromosomes Chromosomes (idic)
Isodicentric chromosomes chromosomes contine two copies of the same centromer (unlike isochromosomes). isochromosomes). One of two centromeres might be inactive, in which case the chromosome is pseudodicentric (psudic). The break break oints oints in in isodi isodicen centric tric chrom chromoso osomes mes are usuall usuall on the the band band adjacent to the centromere on the opposite arm: 46,XX,idic(18)(q11.2) Here, we have an isodicentric chromosome compired of two copies of the entire short arm of chromosome 18, two copies of the centromere, and two copies of the small potion of the long arm between the centromere and band q11.2
Isodicentric chromosome 15 [idic(15)] (right (right). ). Two normal copies chromosome 15, one chromosome comes from the mother and the other from the father (left (left))
Marker Chromosomes (mar) Marker chromosomes are supernumerary, structuarally abnormal chromosomes of which no part can be identified. If any part of such a chromosome is identifiable, it is not a marker but a derivative chromosome. The presence of a “mar” in a karyotype is always by a plus (+) sign. 47,XY,+mar This is a male karyotype with a marker chromosome. 48,XY,+2mar This is a male karyotype with two marker chromosomes. 48,XY,t(5;12)(q13;p12),+21,+mar This discribes a male karyotype with a translocation involving chromosomes 5 and 12, an extra chromosome 21, and a marker chromosome.
Ring chromosomes (r) A structurally abnormal chromosome with two breaks, one on short arm and one the long arm, in which the broken ends are attached to from a circular configuration is a ring chromosome. The net result is deletion of at least the terminal ends arms, and potentially more (most) of either or both arms. 46 X r X This is a female karyotype with only one normal X chromosome and a ring X chromosome with no information on breakpoints. 46,X,r(X)(p22q24) This describe a female karyotype with one normal X chromosome and a ring X chromosome with break and reunion at band p22 and q24. the material distal to both breakpoints is lost.
Deleted Genetic Material
Fusion
Deleted Genetic Material
