In this article we will discuss about:- 1. Meaning of Deficiency in Chromosome 2. Origin of Deficiency in Chromosomes 3. Deletion in Human 4. Chromosome Pairing 5. Uses.
Meaning of Deficiency in Chromosome:
The term deficiency was coined by Bridges in 1917. It may be defined as a structural change resulting in the loss of a terminal acentric chromosome, chromatid or sub-chromatid segment and as a result, loss of the genetic information contained in this segment.
It result from a single break. Another related term deletion was coined by Painter and Muller in 1929. Deletion is a structural change arising due to a loss of an intercalary region of a chromosome; it involves two breaks. However, both the terms are used as synonyms to describe both terminal intercalary losses, and deletion is the most common in usage.
Deficiency can be divided into two types:
(1) Terminal and
In case of terminal deficiency, the lost chromosome segment includes the chromosome end, i.e., telomere, while the chromosome end remains intact in intercalary deletions and a chromosome segment located between the centromere and the telomere is lost (Fig. 12.1).
In certain organisms, terminal deficiencies are more common, e.g., in maize, whereas in certain other organisms like Drosophila, intercalary deficiency is more common.
Origin of Deficiency in Chromosomes:
Deficiency originates spontaneously or it may be induced artificially. Terminal deficiency requires a single break, while the intercalary deficiency requires two breaks (Fig. 12.1). Terminal deficiency may also arise through a misdivision of the centromere which also produces iso-chromosomes.
Most often, one of the two telocentrics produced by the misdivision of a centromere possesses a smaller part of the centromere and, as a result, does not survive. Only the arm of the chromosome possessing the larger part of the centromere survives. This results into the deficiency of the whole arm of the chromosome.
Such deficiencies are tolerated in polyploid species. Sometimes, translocation occurs between A and B chromosomes. B chromosomes are accessory chromosomes and they are not the normal constituent or the genome. Subsequently, loss of B chromosome carrying the trans-located segment of the A chromosome will produce a deficiency for that segment.
Sometimes the broken ends of the sister chromatids fuse together; this results in a dicentric chromatid bridge at the following anaphase. This bridge may break at any position between the two centromeres, as a result, one of the chromosomes may have a rather large deficiency.
Phenotypic Effects of Deficiency in Chromosomes:
1. Large deficiencies are lethal even in the heterozygous condition.
2. The deficiency heterozygotes are hemizygous for the missing loci. In such cases, the recessive alleles of the missing gene express themselves; this phenomenon is called pseudo-dominance.
3. The deficiency may act as a recessive lethal.
In Drosophila, “notched wing” phenotype is produced by a deletion in the X chromosome; this deleted segment carried the w locus for eye colour. Males are hemizygous for the X chromosome genes; as a result, this deletion is lethal in males.
The notched females are hemizygous for the deleted chromosome segment; therefore, the recessive gene for white eye shows pseudodominace. It was found that a loss of the segment of X chromosome containing bands 3C7 resulted into notched phenotype.
Very small deficiencies resemble recessive mutations. Yellow body colour in Drosophila is an example. A small deficiency in the X chromosome involving this locus results into yellow body colour. This locus was found to be located in the bands 1A5-8.
Thus some deletions can produce specific phenotypic effects, like mutant genes. In Drosophila, a number of such effects, acting as dominant alleles, have been observed, e.g., Minute, Delta, Plexate, Beaded, Gull, Notch and several others. Similar studies have led to the conclusion that the salivary gland chromosome “band” or “inter-band” regions may represent genes.
Deficiencies have been observed in maize and several other plants. However, they are mostly restricted in their transmission due to pollen sterility. The male gametophyte is generally nonfunctional due to the presence of deficiency.
The egg on the other hand, can tolerate the effects of deficiency and may remain functional. Minute homozygous deficiencies may be viable and they can produce mutant phenotypes. In maize, there is an example of the location of gene for seedling colour on chromosome 9 by the use of deficiency. In maize, yellow green seedling (yg2) is recessive to normal green seedling (Yg2) character.
The short arm of chromosome 9 possesses a terminal heterochromatic knob and chromomeres which can be observed at pachytene. Deficiencies of different parts occurred in this chromosome due to crossing over between two inverted segments. A comparison of the phenotypes and the deficient parts of chromosome 9 showed that the terminal knob had a small effect on the expression of Yg2 phenotype.
But a loss of the half part of the chromosome adjacent to the knob resulted in white seedlings. From the studies of different combinations of these deficiencies, McClintock in 1944 concluded that Yg2 gene is located in the half portion of the concerned chromomere.
In Drosophila, an example of physical location of genes by means of deficiency concerns the genes for yellow body colour (y) and scute bristles (sc) (reduced or lost bristles). Wild type males were irradiated with 2500 to 3000. r X-ray, and were mated with y (yellow body) and sc (scute) females.
The F1 females with yellow body or scute bristles or both were crossed with y Hw w (yellow, hairy wing, white) males. The salivary gland chromosomes of the Fx flies were examined. The F, females with y and sc phenotype must have received from their fathers a gene mutation or deletion or some other chromosome aberration having y and sc effects.
By comparing the bands on the salivary gland chromosomes, it was found that deletions were associated with a yellow or scute phenotype. The y was located in the bands 1A5-8, while sc was located in the bands 1B3-4 of the X chromosome.
Deletion in Human:
Different types of deletion syndromes have been reported in human. Of these, two syndromes are:
(i) Cri-du-chat syndrome and
These and some other deletion syndromes are briefly described below:
i. Cri-du-chat syndrome (46, XX or XY, 5p–):
This syndrome was described by Lejeune and associates in 1963; since then, several cases have been reported. The main characteristics of the syndrome are, unusual high pitched cry due to abnormalities of larynx, a characteristic fades, and physical and mental retardation. It is caused by a deletion in the short arm of chromosome 5 (5 p–) belonging to the B group.
ii. Anti-Mongolism (46, XX or XY, Gq–):
This syndrome was first described by Lejeune and coworkers in 1964. The main features of this syndrome are developmental retardation, failure to survive and multiple somatic abnormalities. Other features are eye defects, lowest malformed ears and micrognathia.
This syndrome is caused by a deletion in the long arm of a G group of chromosomes. There are many cytogenetic variants of this condition; a complete loss of one chromosome, i.e., monosomic condition for a G group chromosome (45, XX or XY, G–) also produces anti-mongolism.
Some of the other deletion syndromes:
(i) Short arm deletion of chromosome 4 (46, XX or XY, 4 p–):
This syndrome is the result of a deletion in the short arm of chromosome 4. Its phenotypic effects are : developmental retardation and somatic anomalies, extreme ocular hypertelorism, broad flat nose, raised frequency of simple arches, distal 7′ triradius, single transverse palmer crease and certain dermatoglyphic features.
(ii) Short arm deletion of chromosome 18 (46, XX or XY, 18 p–):
This syndrome produces mental and growth retardation.
(iii) Long arm deletion of D chromosome (46, XX or XY, Dq–):
This is caused by the deletion in the long arm of a chromosome of the D group (chromosomes 13, 14, 15). Its general features are similar to those of Patau’s syndrome, i.e., developmental retardation, microphthalmia, skeletal abnormalities and congenital heart disease.
(iv) Long arm deletion of chromosome 18 (46, XX or XY, 18 q–):
This syndrome was first reported by de Grouchy and associates in 1964. The general features of this syndrome are mental retardation, microcephaly, dysplasia of the mid-facial region, eye defects, growth retardation, malformed ear pinnae, and the presence of excess of whorls on finger tips.
An important feature of the human deletion syndromes is that they occur in a greater proportion of females than that of males.
Chromosome pairing in deficiency heterozygotes produces typical pachytene configurations. In the case of terminal deficiency, the terminal region of the normal chromosome remains unpaired (Fig. 12.1), while a loop formation occurs in the normal chromosome at the site of deletion in the case of intercalary deficiency.
In salivary gland chromosomes of Diptera, deletions can easily be recognized and accurately located by studying the chromosome bands. A typical genetic consequence of deficiency is the lack of crossing over in the region of deletion due to the absence of the homologous segment (in the deficiency homologue).
In plants, male gametes carrying the deleted chromosome are generally sterile, hence deficiencies are generally transmitted through the female gamete. Both, zygote and embryo lethality are observed in animals carrying deficiency.
Uses of Deficiency:
1. Deficiency may be used for the study of chromosome pairing and its behaviour during cells division.
2. They may be used for locating a gene on a particular chromosome:
(a) Where deficiency can be transmitted through pollen:
Pollen grains carrying the dominant alleles of the concerned genes are irradiated and used to pollinate a plant homozygous recessive for all the genes. It is proposed to locate these genes on specific chromosomes.
In F1plants carrying deficiency in the concerned region of the chromosome carrying one of these genes will show recessive phenotype for that particular gene due to pseudo-dominance.
This gene can now be assigned to a specific chromosome of the genome by analysing the pachytene configuration of the concerned F1 plants. A typical cross is shown in Fig. 12.2 using gene A as a general representative.
(b) Where deficiency cannot be transmitted through pollen:
In such cases, deficiencies can be used as stocks for locating genes in specific chromosomes. Recombination between a locus and the deficiency can be estimated following a suitable procedure. For example in maize, yellow endosperm (Y) is dominant over white endosperm (y); this gene is located in the long arm of chromosome 6.
McClintock used a stock carrying a terminal deficiency in the long arm of chromosome 6. This deficiency also included the gene pi. Pollen from the plant of Yy genotype and carrying the deficiency in chromosome 6 (the recessive allele y was located in the deficient chromosome) was used to pollinate plants homozygous for the recessive allele y producing white seeds.
The Fx progeny consisted of 534 yellow seeds and 101 white seeds. The y pollen grains produced by the Yy plant will be inviable as they will carry the deficient chromosome 6 (if gene y is located in chromosome 6). Therefore, a crossing over must occur between the gene y and the site of deletion to yield a normal chromosome carrying they allele (Fig. 12.3).
If this expectation were correct, the frequency of white seeds would be much lower than that of the yellow seeds. But if there were no crossing over between the gene and the deficiency, no white seeds would be recovered. In contrast, if the y gene were not located in the deleted chromosome, the yellow and white seeds would be obtained in 1:1 ratio.
In this example, white seeds are only about 16% which is much lower than the 50% expected if y were not located in chromosome 6. It is therefore, concluded that gene y is located in the chromosome 6. The white seeds (16%) must have been produced due to crossing over between the locus v and the deficiency (Fig. 12.3).
3. Deficiency can be used to resolve special problems, such as, the relationship between chiasma and crossing over which had been under dispute for a long time. According to the Chiasma-type theory proposed by Janssens in 1909, chiasma is the result of chromatid exchange.
Brown and Zohary in 1955, gave the proof that chiasma corresponds with chromatid exchange by using a special stock of Liliumformosanum carrying heterozygous deficiency which produced a heteromorphic bivalent.