In 2003 the rules for the nomenclature of chromosome aberrations were updated and rewritten. References to former versions of these rules can be found in Committee for Standardized Genetic Nomenclature in Mice (1981, 1989, 1994, 1996).
Chromosomes are numbered and identified according to the system given by Nesbitt and Francke (1973), Sawyer et al. (1987), Beechey and Evans (1996), and Evans (1996). The word Chromosome should start with a capital letter when referring to a specific chromosome and may be abbreviated to Chr after the first use, e.g., Chromosome (Chr) 1 and Chr 1. The X and Y chromosomes are indicated by capital letters rather than numbers.
Cytogenetic bands are named by capital letters, alphabetically designating the major Giemsa (G)-staining bands from centromere to telomere. Major subdivisions within cytogenetic bands are numbered. Additional subdivisions are designated using a decimal system.
Major G-band designation: Chr 17B Major subdivisions within the Chr 17B band: 17B1, 17B2 Additional subdivision of band 17B1: 17B1.1, 17B1.2, 17B1.3, etc.
Chromosome anomaly symbols are not italicized (unlike gene symbols).
Symbols for chromosome anomalies consist of three parts:
A chromosome anomaly designation begins with a prefix that denotes the type of anomaly. Each prefix begins with a capital letter, with any subsequent letters being lowercase. The accepted prefixes are:
Cen Centromere Del Deletion Df Deficiency Dp Duplication Hc Pericentric heterochromatin Hsr Homogeneous staining region In Inversion Is Insertion MatDf Maternal deficiency MatDi Maternal disomy MatDp Maternal duplication Ms Monosomy Ns Nullisomy PatDf Paternal deficiency PatDi Paternal disomy PatDp Paternal duplication Rb Robertsonian translocation Sp Supernumerary chromosome T Translocation Tc Transchromosomal Tel Telomere Tet Tetrasomy Tg Transgenic insertion (see Rules for Nomenclature of Genes, Genetic Markers, Alleles, and Mutations in Mouse and Rat) Tp Transposition Ts Trisomy UpDf Uniparental deficiency UpDi Uniparental disomy UpDp Uniparental duplication
The chromosome(s) involved in the anomaly should be indicated by adding the appropriate Arabic numerals or letters in parentheses, between the anomaly prefix and the series symbol.
If two chromosomes are involved in a chromosome anomaly, such as translocations and insertions, the chromosomes are separated by a semicolon. In the case of Robertsonian translocations, the chromosomes involved are separated by a period indicating the centromere.
In the case of insertions, the chromosome donating the inserted portion should be given first, followed by the recipient chromosome.
The first and each successive anomaly from a particular laboratory or institution is distinguished by a series symbol, consisting of a serial number followed by the Laboratory Registration Code or Laboratory code of the person or laboratory who discovered the anomaly. The Laboratory code should be the code already assigned for the particular institute, laboratory, or investigator for use with strains that they hold. If there is no preassigned code, one should be obtained from the Institute of Laboratory Animal Research (ILAR) (). Laboratory codes are uniquely assigned to institutes or investigators and are usually three to four letters (first letter upper case, followed by all lower case).
In(2)5Rk inversion involving Chr 2; the 5th chromosome anomaly from T. H. Roderick's lab T(4;X)37H translocation involving Chr 4 and Chr X, the 37th chromosome anomaly from Harwell Rb(9.19)163H Robertsonian translocation involving Chr 9 and Chr 19, the 163rd chromosome anomaly from Harwell Is(7;1)40H insertion of part of Chr 7 into Chr 1, the 40th chromosome anomaly from Harwell
Once the full designation for a chromosome anomaly is written in a document, an abbreviation can be used thereafter. The abbreviation consists of the anomaly prefix plus the serial number designation and Laboratory code. The chromosomal content in parentheses is omitted.
Using the examples from section 2.3:
Full designation Abbreviation In(2)5Rk In5Rk T(4;X)37H T37H Rb(9.19)163H Rb163H Is(7;1)40H Is40H
When an animal carries two or more anomalies that are potentially separable by recombination, the symbols for both (or all) anomalies should be given.
Rb(16.17)7Bnr T(1;17)190Ca/+ + an animal heterozygous for a Robertsonian and a reciprocal translocation, each involving Chr 17. The anomalies are organizationally in "coupling" i.e., the same Chr 17 is involved in both. Rb(5.15)3Bnr +/+ In(5)9Rk an animal heterozygous for a Robertsonian and heterozygous for an inversion. Because they share a common chromosome, Chr 5, the organization of the anomalies is specified as in "repulsion." Rb(10.11)5Rma/+ T(3;4)5Rk an animal that is heterozygous for a Robertsonian translocation and homozygous for an unrelated reciprocal translocation.
When one chromosome anomaly is contained within another or is inseparable from it, the symbols should be combined.
T(In1;5)44H an animal carrying a translocation between Chrs 1 and 5 in which the Chr 1 segment is inverted.
The symbols p and q are used to denote the short and long arms, respectively, of mouse chromosomes. In translocations, breaks in the short arm should be designated with a p, but the q for long arm may be omitted if the meaning is clear. Because mouse autosomes and the X Chromosome are acrocentric, they do not have a short arm other than a telomere proximal to the centromere. Therefore, most rearrangements in mouse chromosomes involve breaks in the long arm (q arm). In mouse, Chr Y has both a p and q arm.
T(Yp;5)21Lub translocation involving a break in the short arm of the Y Chromosome and the long arm of Chr 5; the 21st from Lubeck.
When the positions of the chromosomal breakpoints relative to the G-banded karyotype are known, these are indicated by adding the band numbers, as given in the standard karyotype of the mouse (Evans 1996), after the appropriate chromosome numbers.
T(2H1;8A4)26H reciprocal translocation having breakpoints in band H1 of Chr 2 and band A4 of Chr 8; the 26th from Harwell In(XA1;XE)1H inversion of the region between the breakpoints in bands A1 and E of the X Chromosome; the 1st from Harwell Del(7E1)Tyr8Rl deletion of band 7E1 manifesting as a mutation to albino, Tyrc;the 8th from Russell Is(In7F1-7C;XF1)1Ct inverted insertion of a segment of Chr 7 band F1-C into the X Chromosome at band F1; the 1st from Cattanach
For pericentric inversions the symbols pq and/or appropriate band numbers should be used.
In(8pq)1Rl pericentric inversion involving Chr 8; the 1st from Russell In(8pqA2) pericentric inversion of the region between the short arm and band A2 of the long arm of Chr 8 In(5C2;15E1)Rb3Bnr 1Ct the first inversion found by Cattanach in Rb3Bnr of the region between bands 5C2 and 15E1
The deficiency (Df) and duplication (Dp) nomenclature should be restricted in its use to defining the unbalanced products of chromosome aberrations, i.e., deficient/duplicated chromosomes resulting from malsegregation of reciprocal translocations. Deletions are interstitial losses often, although not always, cytologically visible. Neither of these terms should be applied to small intragenic deletions. The latter give rise to allelic variation in a single locus and are given allele symbols.
Since the 1980s, mouse translocations have been extensively used in imprinting studies to generate uniparental disomies and uniparental duplications (partial disomies) and deficiencies of whole or selected chromosome regions, respectively (reviewed by Cattanach and Beechey 1997 and Beechey 1999). The resulting chromosomal change may be of maternal, paternal, or uniparental (referring to one or the other parent without specification of maternal vs. paternal) origin.
These chromosome anomalies are of three types:
Disomies and duplications of one parental copy imply deficiency of the other parental copy.
The nomenclature for these anomalies includes the affected chromosome in parentheses. The abbreviations, prox (proximal) and dist (distal) can be used to denote the position of the duplication/deficiency relative to the breakpoint of a translocation used to generate the duplication/deficiency. Similarly, if a translocation is used to produce a uniparental disomy or duplication, this can be indicated in the symbol.
MatDi(12) maternal disomy for Chr 12 PatDp(10) paternal duplication for a region of Chr 10 MatDp(dist2) maternal duplication for distal Chr 2 MatDf(7) maternal deficiency for Chr 7 PatDi(11)Rb4Bnr paternal disomy for Chr 11 produced using Robertsonian translocation Rb(11.13)4Bnr MatDp(dist2)T26H maternal duplication for the region of Chr 2 distal to the breakpoint of the reciprocal translocation T(2;8)26H
If cytologically visible deletions are first detected by change in the phenotype produced by a gene (e.g., MgfSl-12H), the gene and allele symbol designation should be included in the chromosome anomaly symbol, e.g,. Del(10)MgfSl-12H1H was originally identified as Sl12H (see Rules for Nomenclature of Genes, Genetic Markers, Alleles, and Mutations in Mouse and Rat).
Trisomies and monosomies should be denoted by the appropriate prefix symbol, followed by the chromosome(s) concerned. If a tertiary aneuploid or partial aneuploid is derived from a translocation, then the chromosome composition (proximal chromosome end; superscripted distal chromosome end) is denoted in parentheses, followed by the serial number and Laboratory code.
Ts16 trisomy for Chr 16 Ts(113)70H trisomy for the proximal end of Chr 1 and the distal end of Chr 13, derived from the translocation T(1;13)70H (also referred to as tertiary trisomy or partial trisomy).
Nullisomy, monosomy, and tetrasomy are denoted similarly.
Transchromosomal is the term used to reference the case where a chromosome, chromosomal fragment, or engineered chromosome from another species exists as a separate, heritable, freely segregating entity or is centromerically fused to an endogenous chromosome. The designation of the additional chromosome is represented parenthetically including the species abbreviation and chromosome from that species, followed by an established line number and an ILAR Laboratory code.
The format for a transchromosomal is: Tc(AAAbb)CCXxx
Tc = transchromosomal AAA = species abbreviation (e.g., HSA=human; MUS=mouse; BOV=bovine) bb = chromosome number of the inserted fragment from the other species CC = line number Xxx = Laboratory code
Tc(HSA21)91-1Emcf transchromosomal, human 21, line 91-1 Elizabeth M. C. Fisher
This is an engineered mouse line containing a fragment of human chromosome 21 as a freely segregating heritable fragment.
The symbol NOR should be reserved for nucleolus organizers. Different organizers should be distinguished by chromosome numbers. Polymorphic loci within the ribosomal DNA region are designated with the root gene symbol, Rnr and the chromosome number (see Rules and Nomenclature of Genes, Genetic Markers, Alleles, and Mutations in Mouse and Rat)
Rnr12 a polymorphic DNA segment that identifies the ribosomal DNA region on Chr 12
The symbol H should be used for heterochromatin visualized cytologically, followed by a symbol indicating the chromosome region involved, in this case c for centromeric, and a number indicating the chromosome on which it lies.
Hc14 pericentric heterochromatin on Chr 14
Variations in size, etc., of any block should be indicated by superscripts, using n for normal or standard, l for large and s for small bands.
Hc14n normal or standard pericentric heterochromatin on Chr 14.
In describing a new variant, a single inbred strain should be named as the prototype or standard strain.
Individual loci or DNA segments mapped within heterochromatin should be symbolized with D- symbols (for details of naming DNA segments, see Rules for Nomenclature of Genes, Genetic Markers, Alleles, and Mutations in Mouse and Rat). A lowercase h follows the D to indicate the DNA locus is a genetic marker for the heterochromatin region.
Dh1H the first DNA segment within the pericentromeric heterochromatin region of Chr 1 discovered at Harwell.
The centromere itself (as opposed to pericentric heterochromatin) should be denoted by the symbol Cen. Individual loci or DNA segments mapped within the centromere region should be symbolized with D- symbols. It should be noted that at present there is no sequence definition for the centromere; Cen refers to the functional unit of the centromere.
The telomere should be denoted by the symbol Tel. The symbol Tel may be substituted for D in a locus symbol that refers to a locus recognized by a telomere consensus sequence probe. Symbols for such loci (mapping to the telomere region) are italicized and consist of three parts:
Tel14q a telomere sequence on Chromosome 14 at the distal chromosome end
Multiple loci assigned to telomeres of individual chromosomes are numbered serially.
Tel14p1 the first telomere sequence mapped at the centromeric end of Chr 14 Tel19q2 the second telomere sequence mapped at the distal end of Chr 19
Telomeric sequences mapped to other chromosome regions should be designated as -rs loci and are sequentially numbered (see Rules for Nomenclature of Genes, Genetic Markers, Alleles, and Mutations in Mouse and Rat and Sawyer et al., 1987).
Tel-rs2 telomere related sequence 2. This sequence maps at approximately 33cM on Chr 8.
When a recognizable and heritable variant in size, staining density, etc. of a particular chromosomal G-band is discovered, this should be indicated by giving the designation of the band affected, in accordance with the standard karyotype of the mouse (Evans 1996), with a superscript to indicate the variant concerned.
Chr 17A2s small A2 band in Chr 17
When a supernumerary band becomes visible, this may be due to a small duplication, and if so should be designated as such. If the supernumerary band is due not to a duplication but to a further resolution within a band then a new band should be designated as a subdivision of the appropriate known band (see Section 1 above).
Chromosomal complements may be described using the type of nomenclature used for human chromosomes when dealing with whole arm changes. In this case the number of chromosomes is specified, followed by a comma and a specification of the whole arm chromosome change. Symbols used to designate these whole arm chromosome changes are:
For mosaics a double slash is used to separate the components of the chromosomal mosaic.
41,XY+13 the normal mouse male complement with an additional copy of Chr 13 39,XO a female mouse complement missing a Chr X 39,XO//41,XYY a mosaic where one component is a female XO and the other a male component carrying an extra Chr Y.
Beechey, C.V., Evans, E.P.:Numerical variants and structural rearrangements, pp. 1452-1506. In: Genetic Variants and Strains of the Laboratory Mouse, Lyon, M.F., Rastan, S., and Brown, S.D.M. (eds.), Third Edition, Volume 2, Oxford University Press, Oxford, 1996.
Beechey, C.V.: Imprinted genes and regions in mouse and human, pp. 303-323. In: Genomic Imprinting: An Interdisciplinary Approach. Results and Problems in Cell Differentiation, Ohlsson R (ed), Springer-Verlag, 1999.
Cattanach, B.M., Beechey, C.V.: Genomic imprinting in the mouse: possible final analysis, pp. 118-145. In: Genomic Imprinting: Frontiers in Molecular Biology, Reik, W., Surani, V. (eds.), Vol 18, IRL Press Oxford, NY, Tokyo 1997.
Committee on Standardized Genetic Nomenclature for Mice, Chair: Lyon, M.F.: Rules for nomenclature of chromosome anomalies, pp. 314-316. In: Genetic Variants and Strains of the Laboratory Mouse, Green, M.C. (ed.), First Edition, Gustav Fischer Verlag, Stuttgart, 1981.
Committee on Standardized Genetic Nomenclature for Mice, Chair: Lyon, M.F.: Rules for nomenclature of chromosome anomalies, pp. 574-575. In: Genetic Variants and Strains of the Laboratory Mouse, Lyon, M.F., A.G. Searle (eds.), Second Edition, Oxford University Press, Oxford, 1989.
Committee on Standardized Genetic Nomenclature for Mice, Chairperson: Davisson, M.T.: Rules and guidelines for genetic nomenclature in mice. Mouse Genome 92 (1994) vii-xxxii.
Committee on Standardized Genetic Nomenclature for Mice, Chairperson: Davisson, M.T. Rules for nomenclature of chromosome anomalies, pp. 1443-1445. In: Genetic Variants and Strains of the Laboratory Mouse, Lyon, M.F., Rastan, S., and Brown, S.D.M. (eds.), Third Edition, Volume 2, Oxford University Press, Oxford, 1996.
Evans, E.P.:Standard normal chromosomes, pp. 1446-1449. In: Genetic Variants and Strains of the Laboratory Mouse, Lyon, M.F., Rastan, S., and Brown, S.D.M. (eds.), Third Edition, Volume 2, Oxford University Press, Oxford, 1996.
Nesbitt, M.N., and U. Francke. 1973. A system of nomenclature for band patterns of mouse chromosomes. Chromosoma 41:145-158.
Sawyer, J.R., M.M. Moore, and J.C. Hozier. 1987. High resolution G-banded chromosomes of the mouse. Chromosoma 95:350-358.