APPENDICES

Chromosome Abnormalities and Genetic Counseling , 3rd Edition

A. Ideograms of Human Chromosomes and Haploid Autosomal Lengths

HAPLOID AUTOSOMAL LENGTH

To determine the (quantitative) amount of a particular segmental imbalance, as a fraction of the haploid autosomal length (HAL), multiply (1) the fraction of the whole chromosome thatthis segment comprises by (2) the HAL of the whole chromosome. The fraction is readily estimated by placing a millimeter rule against the ideogram in Fig. A–1 following. The HAL of the autosome concerned is taken from Table A-1.

For example, considering the imbalance due to the karyotype of the children pictured in the frontispiece and shown in Figure 4-1, what proportion of the HAL does the segment 4q31.3 → qter constitute? First, the segment comprises 18% of the length of chromosome 4: running a millimeter rule alongside the ideogram of chromosome 4 in Figure A–1, the whole chromosome is 110 mm and the segment is 20 mm, and 20/110 = 18%. Second, from the table, chromosome 4 is 6.3% of the total HAL. Thus, 18% of 6.3% = 1.14% of HAL.

Table A-1. Percentage of Haploid Autosomal Length That Each Autosome Constitutes

Chromosome	Percentage of HAL	Chromosome	Percentage of HAL
1	8.44	12	4.66
2	8.02	13	3.74
3	6.83	14	3.56
4	6.30	15	3.46
5	6.08	16	3.36
6	5.90	17	3.25
7	5.36	18	2.93
8	4.93	19	2.67
9	4.80	20	2.56
10	4.59	21	1.90
11	4.61	22	2.04
Source: From Daniel (1979).

Figure A-1. These depictions represent the bands that can be distinguished at a very high level (850 band) of cytogenetic resolution. Different shadings and lengths of bands reflect actual intensities and lengths as observed by the cytogeneticist. (From U. Francke. Digitized and differentially shaded human chromosome ideograms for genomic applications. Cytogenetics and Cell Genetics 65, 206–219, 1994. Courtesy U. Francke and with the permission of S. Karger.)

B. Cytogenetic Abbreviations and Nomenclature

Cytogenetics has its own jargon and fondness for acronyms, and certain abbreviations are regularly used. The following terms are used fairly frequently in this book and in many genetics journals, and should be familiar to the reader:

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AFP	Alpha-fetoprotein
AS	Angelman syndrome
AT	Ataxia-telangiectasia
CGH	Comparative genomic hybridization
CPM	Confined placental mosaicism
CV	Chorionic villus
CVS	Chorionic villus sampling
del	Deletion
DS	Down syndrome
dup	Duplication
ESAC	Extra structurally abnormal chromosome
ESHRE	European Society for Human Reproduction and Embryology
EUCROMIC	European Collaborative Research Group on Mosaicism in CVS
FISH	Fluorescence in situ hybridization
FPS	Fanconi pancytopenia syndrome
FRAXA	Fragile XA syndrome/the chromosomal fragile site
HAL	Haploid autosomal length
ICSI	Intracytoplasmic sperm injection
idic	Isodicentric
inv	Inversion
iso	Isochromosome
IUGR	Intrauterine growth retardation
IVF	In vitro fertilization
kb	Kilobases of DNA
KS	Klinefelter syndrome
Mb	Megabases of DNA
mtDNA	Mitochondrial DNA
NOR	Nucleolar organizing region
PAR	Pseudoautosomal region
PB (1 and 2)	Polar body (first and second)
PCR	Polymerase chain reaction
PCS	Premature centromere separation
PGD	Preimplantation genetic diagnosis
PGD-AS	Preimplantation genetic diagnosis for aneuploidy screening
PND	Prenatal diagnosis
POF	Premature ovarian failure
PWS	Prader-Willi syndrome
rob	Robertsonian translocation
SCE	Sister chromatid exchange
SMC	Supernumerary marker chromosome
TS	Turner syndrome
UPD	Uniparental disomy

More formally, the description of chromosomal constitution in most laboratory reports and in most case reports in the literature follows an internationally accepted format: the International System for Cytogenetic Nomenclature (ISCN, 1995). First, the diploid number is given. Second, the sex chromosome constitution is given. Thereafter, any abnormality or variant is described. Certain abbreviations are used, as listed below. In structural rearrangements, the position of breakpoints is given by reference to the band involved: short or long arm (p or q), region, and band or sub-band(s) within that band. The region is denoted by a digit 1 through 4, the band by a digit 1 through 8, and the sub-band(s) by digit(s) following a “decimal point.” The centromere is p10 or q10. Illustrative examples of commonly described karyotypes follow.

The nomenclature has evolved to accommodate the growing complexity of cytogenetics, with the earlier nomenclatures issued since the first in 1960 often referred to by the name of the city in which the committee met (Denver, London, Chicago, Paris), and subsequently more anonymously as ISCN (year). Published papers from the earlier years will, of course, have used the nomenclature of their time. Many old papers remain a valuable resource, particularly case reports. The reader consulting these may therefore need to adjust, and learn to handle earlier (generally simpler) versions of cytogenetic nomenclature.

SOME ISCN ABBREVIATIONS

add	Additional material of unknown origin
cht	Chromatid
del	Deletion
der	Derivative chromosome
dic	Dicentric chromosome
dim	Deletion, identified by CGH (= diminished)
dup	Duplication
enh	Duplication, identified by CGH (= enhanced)
fis	Fission (at the centromere)
fra	Fragile site
h	Secondary constriction
i	Isochromosome
idem	The same (to avoid repetition of complex description in a mosaic case)
ins	Insertion
dir ins	Direct insertion
inv ins	Inverted insertion
ish	In situ hybridization
inv	Inversion
mar	Marker chromosome
mat	Maternal origin
minus (-)	Loss of a whole chromosome
mos	Mosaic
p	Short arm
pat	Paternal origin
plus (+)	Gain of a whole chromosome
q	Long arm
r	Ring
rcp	Reciprocal translocation
rea	Rearrangement
rec	Recombinant chromosome
rob	Robertsonian translocation
solidus (/)	Separates cell lines in describing mosaics
stk	Satellite stalk
t	Translocation
tan	Tandem
tas	Telomere association
ter	Terminal (end of chromosome arm)
upd	Uniparental disomy

EXAMPLES OF CYTOGENETIC NOMENCLATURE

Normal

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46,XX	Normal female
46,XY	Normal male
46,XX,9qh+	Normal female, additional material in heterochromatic region of chromosome 9 long arm
46,XY,Yqh-	Normal male, deletion of material from heterochromatic region of Y long arm
46,XY,fra(10)(q23.3)	Normal male, fragile site on chromosome 10 long arm at sub-band 23.3

Abnormal

Sex Chromosome Aneuploidies

45,X	Monosomy X (Turner syndrome)
47,XXY	Klinefelter syndrome
47,XXX	Triple X female
47,XYY	XYY “syndrome”
48,XXXX 49,XXXXY	Two of the more common types of polysomy X
47,XXY/46,XY	Mosaic Klinefelter syndrome
45,X/46,XX	Mosaic Turner syndrome

Autosomal Aneuploidies

47,XY, + 21	Trisomy 21 (Down syndrome)
47,XX, + 21/46,XX	Mosaic Down syndrome
47,XX, + 18	Trisomy 18 (Edwards syndrome)
47,XY, + 13	Trisomy 13 (Patau syndrome)
47,XX, + 8/46,XX	Mosaic trisomy 8
47,XY, + 16	Trisomy 16
45,XX, - 21	Monosomy 21

Polyploidies

69,XXY	Triploidy
92,XXXX	Tetraploidy

Deletions

46,XX,del(4)(p15)	Deletion no. 4 short arm (Wolf-Hirschhorn syndrome)
46,XX,del(5)(p13)	Deletion no. 5 short arm (cri du chat syndrome)
46,XX,del(18)(q12)	Deletion no. 18 long arm

Reciprocal Translocations

46,XX,t(4;12) (p14;p13)	Reciprocal translocation between chromosomes 4 and 12, with breakpoints at p14 in chromosome 4 and p13 in chromosome 12
46,XY,der(12)t(4;12) (p14;p13)mat	Unbalanced complement, having received derivative no. 12 in place of normal 12 from translocation carrier mother
47,XX, +der(22) t(11;22)(q23;q11) pat	Unbalanced complement having received derivative 22 as a supernumerary chromosome from translocation carrier father

Whole Arm Reciprocal Translocations

46,t(1;9)(p10;p10)	Balanced carrier of translocation having both breakpoints at the centromeres, with exchange of whole short arms. Translocation chromosomes are 9p/1q and 1p/9q.
46,t(3;4)(p10;q10)	Balanced carrier of translocation having both breakpoints at the centromeres, with exchange of whole short arm of no. 3 and whole long arm of no. 4. Translocation chromosomes are 3q/4q and 3p/4p.

Insertions

46,XY,dir ins(10;8) (q21;q21.2q22)	Direct insertion of segment q21.2 → q22 of chromosome 8 into q21 of chromosome 10. Segment has original orientation to centromere, namely, q21.2 is proximal and q22 distal.
46,XX,inv ins(2) (p13q31q21)	Inverted insertion of segment q31 → q21 into band 2p13. Segment has opposite orientation to centromere, namely, q31 is proximal and q21 distal.

Other

46,XX,r(15)	A ring chromosome of no. 15
46,X,i(Xq)	An isochromosome of the X long arm
46,XX,add(19)(p13)	Additional material of unknown origin attached to band p13 of chromosome 19
46,XY,upd(15)mat	Uniparental disomy for a maternally derived chromosome 15
46,Y,fra(X)(q27.3)	Male with a fragile site in sub-band 27.3 on the X long arm
1(pp)(qqqqqqqqqq)	Multiradial of chromosome 1 comprising two short arms and 10 long arms (see Fig. 19-4)

C. Determining 95 Percent Confidence Limits and the Standard Error

CONFIDENCE LIMITS

The “Exact confidence limits for p” tables available in most books of statistical tables (e.g., Documenta Geigy, 1982, pp. 89–102) are a useful source of data on confidence limits for the sizes of sample geneticists generally collect. Suppose in a kindred, with ascertainment bias having been suitably accounted for, a total of 54 offspring of translocation carriers were abnormal and 49 were phenotypically normal. The frequency for abnormality from this particular sample is 9.3% (5/54). Checking in Documenta Geigy under N = 54, x = 5, we see that the 95% confidence limits are given as 3.08 to 20.3%. In other words, we may take it as close to being sure that the true risk lies in the range 3 to 20%.

STANDARD ERROR

The standard error (SE) is calculated from the simple formula

where a = the number of abnormals, and n = the total number of offspring after ascertainment correction (Stengel-Rutkowski et al., 1988). Thus, for the preceding example

And thus the risk is given as 9.3 ± 3.9%.

Color plates

Figure. No caption available.

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