Lecture 9

Chromosomal aberration: Variation in chromosome number – euploid, aneuploid, types of aneuploids and their origin; Klinefelter syndrome and Turner syndrome

   Cytogenetics is branch of biology devoted to the study of chromosomes and their implications in genetics.

   Chromosomal aberrations:

• Occasionally, spontaneous (without any known causal factor) variations in the structure and number of chromosomes have been observed in nature.

• These variations are called chromosomal aberrations and can be due to either (a) structural changes or (b) numerical changes

Origin of structural aberration

• Chromosomes are structures with definite organization. However, through various means they may be broken and their normal structure disrupted.

• X-rays, atomic radiations and various chemicals are among the agents that can cause breaks in chromosomes.

• Breaks also sometimes occur under natural conditions, where in most instances the reason for breakage is not known. An initially single deviation from the normal can give rise to a whole series of unusual cytological events.

Breakage-fusion-bridge Cycle:

• In the gametophyte and endosperm of corn, ends of chromosomes that have recently been broken behave as though they were “sticky,” as is shown by their tendency to adhere to one another. Extensive studies of broken chromosomes in corn have been made by Barbara Mc Clintock.

• She found that following reduplication of a broken chromosome the two sister chromatids may adhere at the point of previous breakage. The fused sister chromatids would be unable to separate readily. In effect, they constitute a single chromatid with two centromeres, a dicentric chromatid.

• As the centromeres move to opposite poles at anaphase, the dicentric chromatid stretches out, forming a chromatin bridge from one pole toward the other. This bridge eventually breaks, but the break does not always occur at the point of previous fusion. Therefore, chromosomes may be formed that show duplications or deficiencies if compared with an original type. Thus, if the original chromosome is

 C B A

The type

 C B A A is a duplication type, since region A is represented twice.

The type

 C B

 is a deficiency, since region A is absent.

• When a chromosome bridge breaks, perhaps as the result of tension caused by the movement of two centromeres of the dicentric chromatid two new broken ends are formed. Each of these has the same qualities of adhesiveness that gave rise to the original fusion.

• This situation permits repetition of more similar events as described above, in cyclic series. Spontaneous production of chromosome aberrations through breakage-fusion-bridge cycles may occur in this manner for some time. But when a broken chromosome is introduced into the sporophyte generation such cycles cease, as the broken ends heal in the zygote.

Numerical chromosomal aberrations:

• Each species of micro-organisms, plants and animals is characterized by particular chromosome complement or set of genomes, represented once in gametic (haploid) cell i.e. n and twice in somatic (diploid) cells i.e. 2n.

• The term genome refers to a complete set of chromosomes of a diploid species. All the members of a genome are distinct from each other in gene content and often in morphology. Members of a genome do not pair.

• Possession of such sets of chromosomes or genomes, gives a specific chromosome number to each species. But sometimes, some irregularities may occur during mitosis, meiosis or fertilization and may produce cells with variant chromosome number.

• A deviation from the diploid state represents a numerical chromosomal aberration which is often referred to as heteroploidy. Individuals possessing variant chromosome number are known as heteroploidy. Variation in chromosome number (ploidy) may occur through the addition or loss of complete chromosome set or genome (euploidy) or of one or few chromosomes (aneuploidy).

• Thus, numerical changes in chromosomes (heteroploidy) can be mainly of two types:

  •  Euploidy

  • Aneuploidy.

Euploidy: (Greek word; Eu = true or even; ploidy = unit)

• The term euploidy designates a change in chromosome number which involves entire set of chromosomes. Euploids have one or more complete genomes, which may be identical with or distinct from each other.

• The somatic chromosome number of a euploid individual is exact multiple of basic chromosome number of that species. The basic chromosome number refers to the haploid or gametic chromosome number of a diploid species and in case of polyploidy species, the haploid chromosome number of parental diploid species; represented by x. Euploidy includes monoploids, diploids and polyploids.

Monoploids: Monoploids contain a single chromosome set and are characteristically sterile. In other words, monoploids have the basic chromosome number (x) of a species. Monoploids (x) differ from haploids (n) which carry half or gametic chromosome number. In a true diploid species, both monoploid and haploid chromosome number are same (i.e. x=n).

Haploid:  Haploid is a general term used to designate the individuals or tissues with a gametic chromosome number.

Aneuploidy: It is any deviation from a euploid condition. This condition can be expressed either as an addition of one or more entire chromosome or as a loss of such chromosomes to a genomic number. Aneuploidy can be due to:

• Loss of chromosomes in mitotic or meiotic cells due to laggards (lagging chromosomes), which are characterized by retarded movement during anaphase.

• Irregularities of chromosome distribution during meiosis of polyploids with uneven number of basic genomes like triploids and pentaploid.

• The occurrence of multipolar mitosis resulting in irregular chromosome distribution during anaphase.

Aneuploids can be of the following types:

Monosomy:

• The diploid organism which lacks one chromosome of a single homologous pair is called monosomic with genomic formula 2n-1. A monosomic produces two types of gametes n and n-1 because single chromosome without a pairing partner may go to either of poles during meiosis. The monosomics are usually weaker than normal diploids.

• Monosomics are normally found in polyploids and the diploids cannot tolerate them. The polyploids have several chromosomes of same type and therefore, this loss can be easily balanced by homologous or partially homologous chromosomes from other genomes.

• The number of possible monosomics in an organism will be equal to the haploid chromosome number. In common wheat, since 21 pairs of chromosomes are present, 21 possible monosomics are known. These 21 monosomics in wheat were produced by Sears in 1954 in the variety Chinese spring and are being used for genetic studies all over the world.

• Monosomics have been used extensively in wheat breeding for the purpose of chromosome substitution. Double monosomics (2n-1-1) or triple monosomics (2n-1-1-1) could also be produced in polyploids like wheat. In double monosomics the missing chromosomes are non-homologous.

Nullisomy:

• Diploid organisms which have lost a pair of homologous chromosomes are called nullisomics with genomic formula 2n-2. In double monosomy and nullisomy, the chromosome number is same but the genomic formula differs.

• In nullisomy (2n-2), a complete homologous chromosome pair is missing. In double monosomy, (2n-1-1), two chromosomes of different chromosome pairs (one each from two different chromosome pairs) are missing.

• Nullisomics are not usually found in natural populations, but have to be obtained by intercrossing or selfing of monosomics (2n-1). These can occur by fusion of two gametes that are lacking in the same chromosome.

  • Nullisomic series are not of great agronomic importance, but used for genetic studies. They exhibit reduced vigour, fertility and survival.

  • Double nullisomy (2n-2-2) involves loss of two pairs of homologous chromosomes.

  • Monosomics and nullisomics are together known as hypoploids, which refers to loss of one or two chromosomes from the normal diploid.

Trisomy:

• Trisomics are those organisms which have one extra chromosome (2n+1). Since the extra chromosome may belong to any one of the different chromosome pairs, the number of possible trisomics in an organism will be equal to the haploid chromosome number.

• For instance, in barley (2n = 14) the haploid chromosome number is n = 7. Consequently, seven trisomics are possible, in a trisomic, one of the pairs of chromosomes has an extra member and forms a trivalent during anaphase I of meiosis. Two chromosomes will go to one pole and one chromosome will go to another pole. As a result, two types of gametes are formed i.e. n and n+1. This is very common in plants and has variable effects on phenotype.

• In plants, the first case of trisomy was investigated in Jimson weed i.e. Datura stramonium by A.F. Blakeslee and J. Belling in 1924. Datura (2n = 24) normally has 12 pairs of chromosomes in somatic cells. But in an individual, they discovered 25 chromosomes. The size, shape and spine characteristics of seed capsule of this trisomic plant were different from seed capsule of wild type species. Through experimental breeding, Blakeslee and his associates succeeded in producing all 12 possible trisomics.

• When these were grown, each was found to have a distinguishable phenotype that was attributed to extra set of genes present on the extra chromosome contained in each of the 12 pairs of chromosomes.

• An individual having two extra chromosomes each belonging to a different chromosome pair is called double trisomic (2n + 1 + 1).

• Depending on the nature of extra chromosome, simple trisomics are of three types.

  • Primary trisomics: The additional chromosome is normal one in primary trisomics.

  • Secondary trisomics: Trisomics having isochromosome as additional chromosome.

  • Tertiary trisomics: When additional chromosome in a trisomic is translocated one, it is known as tertiary trisomic. The first human trisomic syndrome discovered was the one involving ‘G’ group of chromosomes called Mongolism or Down’s syndrome.

Tetrasomy:

• Tetrasomics have a particular chromosome represented four times. Therefore, the general chromosome formula for tetrasomics is 2n+2. All the 21 possible tetrasomics in wheat are viable.

• Tetrasomics often behave more regularly than the aneuploids with odd number of chromosomes. The four homologues tend to form a quadrivalent at meiosis and disjunction often proceeds fairly regularly, two by two.

• Trisomics and tetrasomics are together known as hyperploids or polysomics, which refers to addition of one or two chromosomes to a single or two different homologous pairs.

Applications of aneuploids: Aneuploids are useful in crop improvement and genetic studies as detailed below:

• Aneuploids have been used to determine the phenotypic effects of loss or gain of different chromosomes.

• They are used to produce chromosome substitution lines. Such lines provide information on the effect of different chromosomes of a variety in the same genetic background.

• They are also used to produce alien addition and alien substitution lines.

• Monosomics are also used in transferring chromosomes with desirable genes from one species to another.

• Aneuploid analysis permits the location of a gene as well as of a linkage group on to a specific chromosome. Monosomics and nullisomics are used for this purpose.

• Studies on nullisomic and tetrasomic combinations made it possible to establish homoeology among the chromosomes of A, B and D genomes of wheat.

• Aneuploids are also useful in identifying the chromosomes involved in translocations (tertiary trisomics).

• Aneuploids are also useful in the preparation of molecular maps. 9) They may be used for obtaining chromosome specific probes. (Probe is a DNA sequence that is used to detect the presence of the same DNA sequence in a test DNA sample).

Klinefelter syndrome:

   Klinefelter syndrome is a genetic condition in males where they have an extra X chromosome, resulting in a 47, XXY chromosome configuration instead of the typical 46, XY. It can lead to various physical, hormonal, and developmental differences, including infertility and reduced testosterone levels. 

Turner syndrome:

    Turner syndrome is a genetic condition in females where one of the X chromosomes is missing or partially missing. This means that instead of having two X chromosomes, individuals with Turner syndrome typically have only one, or one X chromosome that is structurally altered. This can lead to various physical and developmental differences.