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Criteria for the numbering of human chromosomes

Criteria for the numbering of human chromosomes



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What were the criteria devised for the numbering convention employed in human chromosomes? When was it fixed?

Correct me if I am wrong; it appears that chromosome pairs 1 to 22 were originally ordered in terms of perceived structural size, which ended up fitting neatly with the quantity of base pairs (but not with the quantity of genes).

The sex chromosomes in turn were arbitrarily assigned as "pair 23".

Is this sound?

Thanks in advance.


Why do you think it was "fixed?" Here's a nice review of the history of human cytogenetics, which included not only the original image from 1956 but points out a report which comments on the standardization of chromosome number. The autosomes were indeed numbered by length, and the sex chromosomes are traditionally put at the end as they are "numbered" 23 but clearly function quite differently. Gene content was decades away from being known at the time, and honestly isn't even known now. It's also just as arbitrary; simple size is easy enough and makes for rather nice pictures.


Criteria for the numbering of human chromosomes - Biology

Chromosomes are tiny structures inside cells made from DNA and protein. The information inside chromosomes acts like a recipe that tells cells how to function and replicate. Every form of life has its own unique set of instructions, including you. Your chromosomes describe what color eyes you have, how tall you are, and whether you're a boy or a girl.

Chromosomes are found in the nucleus of every cell. Different forms of life have a different number of chromosomes in each cell. Humans have 23 pairs of chromosomes for a total of 46 chromosomes in each cell.

Different chromosomes carry different types of information. For example, one chromosome may contain information on eye color and height while another chromosome may determine blood type.

Within each chromosome are specific sections of DNA called genes. Each gene contains the code or recipe to make a specific protein. These proteins determine how we grow and what traits we inherit from our parents. The gene is sometimes called a unit of heredity.

When we talk about a gene we are referring to a section of DNA. One example of this would be the gene that determines the color of your hair. When we talk about the specific sequence of a gene (like the sequence that gives you black hair versus the sequence that gives you blonde hair), this is called an allele. So everyone has a gene that determines their hair color, only blondes have the allele that makes the hair blonde.

As we mentioned above, humans have 23 different pairs of chromosomes for a total of 46 chromosomes. We all get 23 chromosomes from our mother and 23 from our father. Scientists number these pairs from 1 to 22 and then an extra pair called the "X/Y" pair. The X/Y pair determines if you are a boy or a girl. Girls have two X chromosomes called the XX, while boys have an X and a Y chromosome called the XY.

Chromosomes in Different Animals

Different organisms have different numbers of chromosomes: a horse has 64, a rabbit 44, and a fruit fly has 8.


Homologous Chromosome Function

Two Versions of Each Gene

Diploid organisms, like humans, carry two copies of the genome in each one of their cells. Having two copies of each chromosome, called homologous chromosomes, helps increase both the variety and stability of a species. While each homologous chromosome carries the same genes, they can carry different versions of the gene. Different versions of a gene are called alleles.

This means that your cells will typically produce 2 versions of every protein encoded by the DNA. Some versions will work better than others. Further, the combination of good and bad proteins produces different phenotypic effects that increase the variety within a population. Some alleles have a dominant/recessive relationship, in which the dominant gene is the only one that shows. Others have more complex relationships, and different combinations of alleles can produce vastly different effects on an organism. This is important because variety helps populations survive in the face of environmental changes.

Homologous Recombination

Lastly, homologous chromosomes take part in a process known as homologous recombination during the formation of gametes. This process is also known as “crossing over”, because parts of the homologous chromosomes are exchanged when they come into close contact. The chromosomes contain the same genes, which are generally the same length and size. These sections can easily be transferred between chromosomes. The image below shows recombination:

In this image, each chromosome has already been replicated in preparation for meiosis. However, two of the chromatids have exchanged genetic material. This process is extremely important for the creation and maintenance of variety within a population. For instance, if red is the paternal chromosome and blue is maternal, the genes they carry will no longer be linked. Just because your father had blue eyes and black hair does not mean you will automatically inherit these traits. Homologous recombination ensures that traits are randomly mixed together, from both parental sources.


Karyotype, Karyotyping and Preparation of Idiogram

All species are characterized by a set of chromosomes to carry their genetic information. The chromosomal composition of each species has a number of characteristics. The Karyotype is a set of characteristics that identifies and describes a particular set of chromosome. These characteristics which are described by a karyotype are:-

(1). The chromosome number
(2). Relative size of different chromosomes
(3). Position of centromere and length of chromosomal arms
(4). Presence of secondary constrictions and satellites
(5). Banding pattern of the chromosome
(6). Features of sex chromosomes

What is Karyotyping? How to Prepare the Karyotype of Human?

Ø The process of preparation of the karyotype of a species is called Karyotyping.

Ø Karyotyping is now most commonly used in clinical diagnosis and clinical genetics.

Ø Karyotype is prepared from the microphotographs of metaphase chromosomes.

Ø The metaphase chromosome is selected because at this stage the chromosome will have maximum condensation (maximum thickness).

Ø At metaphase stage, the chromosomes will be visible through an ordinary laboratory microscope.

Ø For the clinical karyotyping, the sample materials used may be cells from biopsies, bone marrow cells, blood cells or cells from amniotic fluid or chorionic villus.

Ø The sample cells were first cultured on artificial medium with suitable growth regulators.

Ø The then the cells are arrested at their mitotic metaphase phase by treating with Colchicine.

Ø Colchicine will arrest the cells at metaphase stage since it prevents the formation of spindle fibres.

Ø In the absence of spindle fibres, the metaphase stage cannot proceed to anaphase.

Ø Then the cells were fixed with suitable fixative and treated with specific stains to produce characteristic banding patterns in the chromosomes.

Ø Specific staining or banding techniques are used to identify the homologous pairs of chromosomes within the cells.

Ø Cells are then observed through the microscope and the photographs of the chromosomes were taken.

Ø The individual chromosomes are cut out from the microphotographs and then they are lined up by size with their respective partners to form the karyogram

Ø A uniformly accepted pattern is used for the arrangement of chromosomes in the preparation of karyogram.

Ø In a karyotype, the chromosomes of the organism are ordered in a series of its decreasing size (largest chromosome at first and smallest at last).

Ø In the case of human, the autosomes are numbered from 1 to 22 and arranged in the order of decreasing size.

Ø Sex chromosomes are arranged after the autosomes.

Ø Chromosomes in the karyogram are aligned along a horizontal axis shared by their centromeres.

Ø Individual chromosomes are always depicted with their short ‘p’ arms at the top, and their long ‘q’ arms at the bottom.

Ø The centromeric index is also noted in karyotype analysis.

Ø Centromeric index is the ratio of the length of long and short arms of the chromosome.

What is an Idiogram?

Ø The diagrammatic representation of a karyotype of a species is called Iiogram.

What are the Significance / Importance of Karyotype and Karyotyping?

Ø Karyotypes of different species can be easily compared.

Ø Similarities in the karyotypes represent the evolutionary relationship.

Ø Karyotypes can be used to solve taxonomic disputes.

Ø The karyotype can indicate primitive and advanced features of an organism.

Ø The karyotype of an organism may be symmetric or asymmetric.

Ø A symmetric karyotype possesses more or less similar sized and shaped chromosomes.

Ø An asymmetric karyotype will have huge differences in small and large chromosomes and contain less metacentric chromosomes.

Ø A symmetric karyotype is considered as primitive whereas, an asymmetric karyotype is considered as advanced.

Ø The zygomorphic flowers in plants are associated with asymmetric karyotype.

Ø Some species may have special characteristics in their karyotypes such as mouse has acrocentric chromosomes and many amphibians have only metacentric chromosomes.

Significance of Clinical Karyotype and Clinical Karyotyping of Human Chromosomes:

Ø Nowadays, the Karyotyping frequency used in clinical diagnosis.

Ø The karyotype provides the structural features of each chromosome in an individual.

Ø A clinical cytologist can analyze the karyotype an individual and can determine the gross genetic changes.

Ø Karyotype reveals the numerical anomalies of the chromosomes such as aneuploidy due to trisomy at 21st chromosome (Down syndrome) trisomy at sex chromosome- XXY (Klinefelters syndrome), monosomy at sex chromosome- XO (Turner syndrome) etc.

Ø Karyotypic analysis can also reveal the structural anomalies of the chromosome such as deletions, duplication, inversion and translocations.

Ø Thus karyotypic analysis can give important diagnostic information in sex determination, detection of birth defects, genetic disorders and detection of some cancers.

Modern methods in the Preparation of Karyotype

@. Fluorescence in-situ Hybridization (FISH) is used in modern research for the preparation of Karyotypes.

@. FISH provide accurate details of the chromosome even at minute scale.

@. FISH preparations of chromosomes are visualized by Fluorescence Microscope


Evolutionary Explanations of Gender

As the evolutionary approach is a biological one, it suggests that aspects of human behavior have been coded by our genes because they were or are adaptive.

A central claim of evolutionary psychology is that the brain (and therefore the mind) evolved to solve problems encountered by our hunter-gatherer ancestors during the upper Pleistocene period over 10,000 years ago.

The evolutionary approach argues that gender role division appears as an adaptation to the challenges faced by the ancestral humans in the EEA (the environment of evolutionary adaptation).

The mind is therefore equipped with ‘instincts’ that enabled our ancestors to survive and reproduce.

The two sexes developed different strategies to ensure their survival and reproductive success. This explains why men and women differ psychologically: They tend to occupy different social roles.

To support the evolutionary perspective, the division of labour was shown to be an advantage. 10,000 years ago there was division of labour between males and females. Men were the hunter gathers, breadwinners, while the mother was at home acting as the ‘angel of the house’ and looking after the children.

Hunting for food required speed, agility, good visual perception. So men developed this skill.

If a women was to hunt, this would reduce the group’s reproductive success, as the woman was the one who was pregnant or producing milk. Although, the women could contribute to the important business of growing food, making clothing and shelter and so on.

This enhances reproductive success but it also important in avoiding starvation – an additional adaptive advantage.

Critical Evaluation

Deterministic approach which implies that men and women have little choice or control over their behaviors: women are natural ‘nurturers’ and men are naturally aggressive and competitive.

The consequence are that in modern society equal opportunities policies are doomed to fail as men are ‘naturally’ more competitive, risk taking and likely to progress up the career ladder.


The gene and protein catalogue of chromosome 19

An automated pipeline of evidence-based and ab initio methods was used to place gene model transcripts on the underlying genomic sequence. Subsequent to this, each transcript was manually reviewed using a combination of human-expressed sequence evidence (messenger RNA and expressed sequence tags (ESTs)) and homology to known genes in humans, mice and other organisms. Additional genes were identified manually from underlying experimental data. Ultimately, a total of 1,461 protein-coding regions were verified as valid gene loci (see Supplementary S2). These loci contain 2,341 full-length (or nearly full-length) transcripts, as well as partial evidence for additional splice variants as discussed below. We placed loci in the following three categories: (1) ‘known’ genes that correspond to RefSeq genes 23 , human complementary DNA or protein sequences (2) ‘novel’ or previously unidentified loci that have an open reading frame (ORF) greater than 100 amino acids, and/or are identical to a spliced human EST, and/or have homology to known genes or proteins (all species) and (3) ‘pseudogenes’, which have sequence similar to genes or proteins found elsewhere in the genome but lack the introns present in the original version (processed) and/or have a disrupted or partial ORF. Transcripts for which a unique ORF could not be determined and putative genes (ab initio models) with no supporting experimental evidence were not considered valid.

We identified 1,320 known loci based on 1,551 RefSeq genes and other nearly full-length cDNA sequences in GenBank that mapped to chromosome 19. On the basis of EST evidence, we were able to extend 60% of these RefSeq transcripts by more than 50 nucleotides at the 5′ and/or 3′ ends while maintaining the original ORF. A total of 41% of the RefSeq loci were extended at the 5′ end, more accurately locating the transcriptional start site for these transcripts. A total of 88% of the transcripts end with a stop in the final exon/untranslated region.

We found evidence for 141 novel loci for which RefSeq genes were not available. These loci are supported by other nearly full-length cDNA sequences, one or more spliced ESTs and/or similarity to known human or mouse sequences. Within this group are 58 human loci modelled using orthologous mouse cDNA sequences. Transfer RNA genes are one of the best-understood non-protein-coding RNA genes with respect to function. We confidently predicted 11 tRNA genes and three tRNA pseudogenes, in stark contrast with the 157 tRNAs found on the p arm of chromosome 6 (ref. 17).

The largest gene on chromosome 19 is the alpha 1A subunit of the P/Q-type voltage-dependent calcium channel (CACNA1A), which extends over more than 300 kilobases (kb) and contains 47 exons. The transcript with the most exons is the skeletal muscle ryanodine receptor (RYR1), which has 105 exons spread over nearly 154 kb. The largest exon on the chromosome is 21,693 bp and is found within the MUC16 gene, a gene encoding an unusually large transmembrane glycoprotein with a role in embryonic development and neoplastic transformation 24 .

Alternative splicing

We characterized the extent of alternative splicing based on the existing cDNA/EST data. Considering only mRNA sequences in GenBank, we identified 2,341 distinct chromosome 19 transcripts that provided an average coverage of 1.6 annotated transcripts per locus (see Supplementary S2). These mRNAs provide strong evidence for alternative splicing of 568 (39%) of the 1,461 annotated gene loci, with each having two or more associated transcripts. Furthermore, an additional 452 genes have at least one EST sequence overlapping with non-annotated exons and also contain flanking canonical splice sites at the genomic locus. Thus, existing experimental data support alternative splicing for a minimum of 1,020 of the genes (70%) on chromosome 19.

It is likely that an even larger fraction of chromosome 19 genes are subject to some form of alternative splicing. As most of our conclusions are based on existing transcribed sequence data, the depth of the EST database seems to be a limiting factor. In fact, of the 184 genes with a total of 500 or more overlapping ESTs, 181 (98%) displayed low-frequency alternative transcripts. Thus deeper EST clone coverage would probably show that a very large fraction of loci can exhibit alternate splicing. Recent studies support this conclusion 25 .

Pseudogenes

We identified 321 pseudogenes on chromosome 19 (see Supplementary S3). Of these, 177 (55%) were classified as ‘processed’ pseudogenes, that is, products of viral retrotransposition events involving spliced messenger RNAs that can frequently be identified by the absence of introns that are present in the parent locus and by the presence of poly(A) stretches embedded in the adjacent genomic sequence. Forty-six (14%) pseudogenes probably arose from genomic duplication events, displaying remnants of introns from the parent locus. An additional 98 (31%) pseudogenes were classified as potential pseudogene fragments owing to their partial nature.

A total of 70 (22%) of the 321 pseudogenes on chromosome 19 contain uninterrupted, but partial, ORFs and probably represent young processed pseudogenes that have not had sufficient time to accumulate mutations to disrupt their ORF, but may also have retained some function. Of the 22 olfactory receptor loci annotated as pseudogenes, four contain a complete ORF. Recent studies have shown that a significant fraction of putative olfactory receptor pseudogenes in the genome are segregating as alleles with intact, presumably functional copies in the human population 26 . Whether any olfactory receptor, or other, pseudogenes on chromosome 19 also vary in humans between such potential functional and non-functional states remains to be explored experimentally.

Gene families and duplication analysis

Chromosome 19 is notable for the prevalence of duplication structures of two types: tandemly clustered gene families and large segmental duplications. As to the latter, chromosome 19 shows evidence of extensive genomic duplication with 7.35% of the sequence sharing sequence homology to more than one location in the genome (Fig. 3 see also Supplementary S4). In contrast, whole-genome estimates of segmental duplication predict 5–6% duplicated sequence using the same alignment parameters (≥ 1 kb length ≥90% sequence identity) 1 . This enrichment on chromosome 19 is predominantly due to an increase in intrachromosomal duplications (6.20% of the sequence) rather than interchromosomal duplications (1.69% of the sequence). Using sequence divergence as a surrogate of evolutionary age, these data indicate that most of the tandem expansions of duplications on chromosome 19 occurred much earlier (30–40 million years ago) when compared with the more recent interchromosomal duplication events. The most marked feature of the segmental duplication pattern on chromosome 19 is the pattern of large intrachromosomal duplications (> 90% sequence identity) clustered in tandem arrangement (Fig. 3 see also Supplementary S5).

a, Large (> 20 kb), highly similar (> 95%) intrachromosomal (blue) and interchromosomal (red) segmental duplications are shown for chromosome 19. Chromosome 19 is drawn at a greater scale relative to the other chromosomes. Gene clusters detected in duplicated sequences (> 1 kb with identity >90%) are represented as light blue bars below the chromosome 19 sequence. A, B, ZNF genes C, cytochrome P450 D, pregnancy-specific α-1-glycoprotein (PSG) E, chorionic gonadotropin β-peptide (CGB) F, leukocyte immunoglobulin-like receptor G, killer cell immunoglobulin-like receptor. b, Sequence similarity of segmental duplications. For all pairwise alignments, the total number of aligned bases was calculated and binned based on per cent sequence identity. Sequence identity distributions for interchromosomally (red) and intrachromosomally (blue) duplicated bases are shown.

More than 25% of the genes on chromosome 19 are members of large, well-defined, tandemly clustered gene families (Fig. 4 and Table 2). Considerable evidence has documented the existence of lineage-specific changes within these and other tandemly clustered families due to ongoing gene duplication, deletion and mutational events 27,28,29,30,31,32,33,34 . These clustered sets of paralogues therefore represent a potentially rich source of genetic diversity, and because of their prevalence, chromosome 19 has an especially dynamic evolutionary history. The largest group of such genes on chromosome 19 encodes Krüppel-type (or C2H2) zinc finger transcription factor (ZNF) proteins, with 266 of the approximately 800 total human genes of this type located primarily within 11 large familial clusters 27,29 . Chromosome 19 contains members of several different ZNF gene subfamilies but most of the clustered genes belong to the KRAB-ZNF subtype (Table 2). One large cluster of ZNF genes, located in the pericentromeric region of the short arm, is exclusive to and arose early in the primate lineage 30 . A unique aspect of this region is the admixture of classical centromeric β-satellite sequences with the ZNF genes. A total of 27 blocks of β-satellite repeat (each ranging from 10 to 50 kb mean = 22 ± 8 kb) map immediately distal to the centromeric α-satellite sequence. These blocks are located throughout the first 4 Mb of the pericentromeric region of 19p12 with an average of 114 kb separating each β-satellite block. Embedded between most of these β-satellite blocks are 1 to 2 KRAB-ZNF genes, indicating that these structures were coordinately duplicated 30 .

Known genes (November 2003) were downloaded from the UCSC browser (http://genome.ucsc.edu) and plotted relative to the relative chromosome size (minus the centromere). Yellow triangles (clustered loci) indicate genes in tandem duplications, whereas blue diamonds (unique loci) indicate loci that are not duplicated in a tandem manner. Green circles (all loci) represent the sum of clustered and unique loci. A subset of the clustered loci that does not involve the KRAB-Kruppel ZNF genes is shown as red squares (non-ZNF clustered loci). As well as having the highest number of genes, chromosome 19 also has the largest number of genes contained in tandem gene families.

Human chromosome 19 also carries a large collection of genes encoding receptor proteins with immunoglobulin-like domains. Genes of the closely related leukocyte immunoglobulin-like receptors (LILRA and LILRB), the leukocyte-associated immunoglobulin-like receptors (LAIR) and the killer cell immunoglobulin receptors (KIR) are found together in the leukocyte cluster region (LCR) of 19q13.4. The proteins encoded by these loci function as receptors for specific classes of antigens on the surface of various types of immune cells. As with the ZNF and olfactory receptor (OR) genes, the LAIR, LILR and KIR gene families differ extensively in their relative numbers and types between different vertebrate lineages. The variety of different immunoglobulin-like receptor proteins may define some of the major differences in strategies adopted by particular lineages to combat infectious agents and antigens encountered in different environments 31 . The KIR gene family arose recently in the primate lineage, and consistent with this, the repertoire of this gene family varies both in gene number and type even between individual humans. Specific KIR haplotypes have been shown to determine differential susceptibility to immune-related diseases, and are associated with differential rates of progression to AIDS in HIV-infected individuals 32 . The KIR haplotype represented in the public human genome sequence corresponds to the most commonly occurring haplotype in the Caucasian population, called A-1D (ref. 32). This carries nine of the seventeen previously described KIR family members, including a known deletion variant of the KIRDS4 locus, KIR2DS4.

Several other large and evolutionarily diverse gene clusters exist on the chromosome, all with diverse evolutionary histories and involvement in various medical conditions. In addition to the LRC family genes, of particular medical importance are the rapidly evolving cytochrome P450 subfamily II genes (CYP2) 33 involved in the metabolism of steroid hormones, carcinogens and other substances, and the kallikrein (KLK) 34 serine protease family, associated with tumour progression. The positions, size and functions of these gene families are summarized in Table 2.


Criteria for the numbering of human chromosomes - Biology

Source: image on left from the GeneMap'99 illustration of Chromosome 18. Image on right from the CCAP Web page on "Recurrent Aberration Data."

Each chromosome arm is divided into regions, or cytogenetic bands, that can be seen using a microscope and special stains. The cytogenetic bands are labeled p1, p2, p3, q1, q2, q3, etc., counting from the centromere out toward the telomeres. At higher resolutions, sub-bands can be seen within the bands. The sub-bands are also numbered from the centromere out toward the telomere.

For example, the cytogenetic map location of the CFTR gene is 7q31.2, which indicates it is on chromosome 7, q arm, band 3, sub-band 1, and sub-sub-band 2.

The ends of the chromosomes are labeled ptel and qtel. For example, the notation 7qtel refers to the end of the long arm of chromosome 7.

Strachan, T. and Read, A.P. 1999. Human Molecular Genetics, 2nd ed. New York: John Wiley & Sons.

GeneMap'99 (click on a chromosome number).

The CCAP Web page on "Recurrent Aberration Data" (click on a chromosome number), based on a genome-wide map of chromosomal breakpoints in human cancer by Drs. Mitelman, Mertens, and Johansson.


Criteria for the numbering of human chromosomes - Biology

Chairperson: Cynthia Smith
(e-mail:[email protected])

To see previous versions of these guidlelines (last revised in November 2013), click here.

Table of Contents

1. General Guidelines for Designating Chromosomes

Mouse 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.

Examples:
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.

2. Symbols for Chromosome Anomalies

Chromosome anomaly symbols are not italicized (unlike gene symbols).

  • A prefix defining the type of anomaly
  • Specifically formatted information indicating the chromosomes involved
  • A series number and Laboratory code designation that uniquely identifies the anomaly

2.1 Prefix

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:

CenCentromere
DelDeletion
DfDeficiency
DpDuplication
HcPericentric heterochromatin
HsrHomogeneous staining region
InInversion
IsInsertion
IsoIsochromosome
MatDfMaternal deficiency
MatDiMaternal disomy
MatDp Maternal duplication
MsMonosomy
NsNullisomy
PatDfPaternal deficiency
PatDiPaternal disomy
PatDpPaternal duplication
RbRobertsonian translocation
TTranslocation
TcTranschromosomal
TelTelomere
TetTetrasomy
TgTransgenic insertion (see Rules for Nomenclature of Genes, Genetic Markers, Alleles, and Mutations in Mouse and Rat)
TpTransposition
TsTrisomy
UpDfUniparental deficiency
UpDiUniparental disomy
UpDpUniparental duplication

2.2 Designating the chromosomes involved in an anomaly

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.

2.3 A series number and Laboratory code designation that uniquely identifies the anomaly

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. Each type of chromosomal anomaly from a given laboratory will have its own series of serial numbers (see examples). 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) ( http://dels.nas.edu/global/ilar/lab-codes). Laboratory codes are uniquely assigned to institutes or investigators and are usually three to four letters (first letter uppercase, followed by all lowercase).

Examples:
Del(9)4Hdeletion involving Chr 9, the 4 th deletion from Harwell
In(15)4Hinversion involving Chr 15, the 4 th inversion from Harwell
Is(131)4Hinsertion of part of Chr 13 into Chr 1 the 4 th insertion from Harwell
In(5)2Rkinversion involving Chr 5 the 2 nd inversion from T.H. Roderick's lab
Rb(3.15)2Rk Robertsonian translocation involving Chr 3 and Chr 15, the 2 nd Robertsonian translocation from T.H. Roderick's lab.
Iso(6)1Hisochromosome 6, the 1 st isochromosome from Harwell

Note: As mouse chromosomes are all acrocentric, with the exception of Chr Y, the p and q arm designations standard for human chromosomes are not used. For mouse Chr Y, p and q are appended as required. Example: Iso(Yq).

2.4 Abbreviating chromosome anomalies

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:

2.5 Symbols for multiple chromosome anomalies

When an animal carries two or more anomalies that are potentially separable by recombination, the symbols for both (or all) anomalies should be given.

Examples:
Rb(16.17)7Bnr T(117)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(34)5Rk an animal that is heterozygous for a Robertsonian translocation and homozygous for an unrelated reciprocal translocation.

2.6 Symbols for complex chromosome anomalies

When one chromosome anomaly is contained within another or is inseparable from it, the symbols should be combined.

2.7 Designating chromosomal breakpoints

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.

Example:
T(Yp5)21Lub translocation involving a break in the short arm of the Y Chromosome and the long arm of Chr 5 the 21 st from Lubeck.

2.7.1 Defining the chromosomal band

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.

Examples:
T(2H18A4)26Hreciprocal translocation having breakpoints in band H1 of Chr 2 and band A4 of Chr 8 the 26 th from Harwell
In(XA1XE)1Hinversion of the region between the breakpoints in bands A1 and E of the X Chromosome the 1 st from Harwell
Del(7E1)Tyr8Rldeletion of band 7E1 manifesting as a mutation to albino, Tyr c the 8 th from Russell
Is(In7F1-7CXF1)1Ct inverted insertion of a segment of Chr 7 band F1-C into the X Chromosome at band F1 the 1 st from Cattanach

For pericentric inversions the symbols pq and/or appropriate band numbers should be used.

Examples:
In(8pq)1Rlpericentric inversion involving Chr 8 the 1 st from Russell
In(8pqA2)pericentric inversion of the region between the short arm and band A2 of the long arm of Chr 8
In(5C215E1)Rb3Bnr 1Ct the first inversion found by Cattanach in Rb3Bnr of the region between bands 5C2 and 15E1

2.8 Deficiencies and deletions as chromosomal anomalies

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.

2.9 Imprinting and chromosomal anomalies

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.

  • Disomy - two copies of a chromosome derived from one parent
  • Duplications - two copies of a chromosome region derived from one parent
  • Deficiencies - missing segments of a particular chromosome region originating from one parent

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.

Examples:
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)Rb4Bnrpaternal 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(28)26H

2.10 Deletions identified through phenotypic change

If cytologically visible deletions are first detected by change in the phenotype produced by a gene (e.g., Mgf Sl-12H ), the gene and allele symbol designation should be included in the chromosome anomaly symbol, e.g,. Del(10)Mgf Sl-12H 1H was originally identified as Sl 12H (see Rules for Nomenclature of Genes, Genetic Markers, Alleles, and Mutations in Mouse and Rat).

2.11 Chromosomal aneuploidy

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.

Example:
Ts16trisomy for Chr 16
Ts(1 13 )70H trisomy for the proximal end of Chr 1 and the distal end of Chr 13, derived from the translocation T(113)70H (also referred to as tertiary trisomy or partial trisomy).

Nullisomy, monosomy, and tetrasomy are denoted similarly.

2.12 Transchromosomal anomalies

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
Example:
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.

3. Variations in Heterochromatin and Chromosome Banding

3.1 Nucleolus organizers

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).

Example:
Rnr12a polymorphic DNA segment that identifies the ribosomal DNA region on Chr 12

3.2 Pericentric heterochromatin

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.

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.

In describing a new variant, a single inbred strain should be named as the prototype or standard strain.

3.3 Loci within heterochromatin

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.

Example:
Dh1Hthe first DNA segment within the pericentromeric heterochromatin region of Chr 1 discovered at Harwell.

3.4 Centromeres

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.

3.5 Telomeres

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:

  • The letters Tel (for telomere)
  • A number denoting the chromosome
  • A letter denoting the centromeric or distal end of the chromosome, namely p for centromeric and q for distal (derived from p and q for short and long arms, respectively).

Multiple loci assigned to telomeres of individual chromosomes are numbered serially.

Examples:
Tel14p1the first telomere sequence mapped at the centromeric end of Chr 14
Tel19q2the 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).

3.6 G-band polymorphisms

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.

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).

4. Use of Human Chromosome Nomenclature

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:

  • "+" to indicate the presence of a specific additional autosome
  • "–" to indicate the absence of a specific autosome
  • "O" to indicate a missing sex chromosome
  • Additional Xs or Ys to indicate supernumerary sex chromosomes

For mosaics a double slash is used to separate the components of the chromosomal mosaic.


What are chromosome abnormalities?

There are many types of chromosome abnormalities. However, they can be organized into two basic groups: numerical abnormalities and structural abnormalities.

Numerical Abnormalities: When an individual is missing one of the chromosomes from a pair, the condition is called monosomy. When an individual has more than two chromosomes instead of a pair, the condition is called trisomy.

An example of a condition caused by numerical abnormalities is Down syndrome, which is marked by mental retardation, learning difficulties, a characteristic facial appearance and poor muscle tone (hypotonia) in infancy. An individual with Down syndrome has three copies of chromosome 21 rather than two for that reason, the condition is also known as Trisomy 21. An example of monosomy, in which an individual lacks a chromosome, is Turner syndrome. In Turner syndrome, a female is born with only one sex chromosome, an X, and is usually shorter than average and unable to have children, among other difficulties.

Structural Abnormalities: A chromosome's structure can be altered in several ways.

Deletions: A portion of the chromosome is missing or deleted.

Duplications: A portion of the chromosome is duplicated, resulting in extra genetic material.

Translocations: A portion of one chromosome is transferred to another chromosome. There are two main types of translocation. In a reciprocal translocation, segments from two different chromosomes have been exchanged. In a Robertsonian translocation, an entire chromosome has attached to another at the centromere.

Inversions: A portion of the chromosome has broken off, turned upside down, and reattached. As a result, the genetic material is inverted.

Rings: A portion of a chromosome has broken off and formed a circle or ring. This can happen with or without loss of genetic material.

Most chromosome abnormalities occur as an accident in the egg or sperm. In these cases, the abnormality is present in every cell of the body. Some abnormalities, however, happen after conception then some cells have the abnormality and some do not.

Chromosome abnormalities can be inherited from a parent (such as a translocation) or be "de novo" (new to the individual). This is why, when a child is found to have an abnormality, chromosome studies are often performed on the parents.

There are many types of chromosome abnormalities. However, they can be organized into two basic groups: numerical abnormalities and structural abnormalities.

Numerical Abnormalities: When an individual is missing one of the chromosomes from a pair, the condition is called monosomy. When an individual has more than two chromosomes instead of a pair, the condition is called trisomy.

An example of a condition caused by numerical abnormalities is Down syndrome, which is marked by mental retardation, learning difficulties, a characteristic facial appearance and poor muscle tone (hypotonia) in infancy. An individual with Down syndrome has three copies of chromosome 21 rather than two for that reason, the condition is also known as Trisomy 21. An example of monosomy, in which an individual lacks a chromosome, is Turner syndrome. In Turner syndrome, a female is born with only one sex chromosome, an X, and is usually shorter than average and unable to have children, among other difficulties.

Structural Abnormalities: A chromosome's structure can be altered in several ways.

Deletions: A portion of the chromosome is missing or deleted.

Duplications: A portion of the chromosome is duplicated, resulting in extra genetic material.

Translocations: A portion of one chromosome is transferred to another chromosome. There are two main types of translocation. In a reciprocal translocation, segments from two different chromosomes have been exchanged. In a Robertsonian translocation, an entire chromosome has attached to another at the centromere.

Inversions: A portion of the chromosome has broken off, turned upside down, and reattached. As a result, the genetic material is inverted.

Rings: A portion of a chromosome has broken off and formed a circle or ring. This can happen with or without loss of genetic material.

Most chromosome abnormalities occur as an accident in the egg or sperm. In these cases, the abnormality is present in every cell of the body. Some abnormalities, however, happen after conception then some cells have the abnormality and some do not.

Chromosome abnormalities can be inherited from a parent (such as a translocation) or be "de novo" (new to the individual). This is why, when a child is found to have an abnormality, chromosome studies are often performed on the parents.


Acknowledgments

The authors dedicate this paper to the 80th anniversary of Professor F. Vogel. We thank Marion Cremer for kindly contributing her 3D analysis of radial HSA 18 and 19 CT arrangements in nuclei of cycling amniotic fluid cells (Figure S8D). We appreciate the technical support of Leica (Cambridge, United Kingdom), SVI (Hilversum, Netherlands), ZeissVision (Hallbergmoos, Germany), and T.I.L.L.-Photonics (Munich, Germany), and we thank Adrian Sumner (North Berwick, United Kingdom) for editorial services. We acknowledge very helpful discussions with Joachim Walter (T.I.L.L.-Photonics), Rainer Heintzmann (MPI for Biophysical Chemistry, Göttingen, Germany), and Jörg Langowski (DKFZ, Heidelberg, Germany). We are indebted to Joanna Bridger and Wallace Marshall, as well as two anonymous reviewers for their helpful comments. This work was supported by the Deutsche Forschungsgemeinschaft (Sp460/2–1, Cr59/20, and Cr60/19) and the German–Israeli Foundation for Research and Technology (G-112–207.04/97).


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