CHROMOSOMAL ABBERATIONS

A SEMINAR REPORT

SUBMITTED TO

DEPARTMENT OF BIOTECHNOLOGY

ICG

IIS UNIVERSITY

FOR PARTIAL FULFILMENT OF DEGREE OF

MASTER OF SCIENCE IN BIOTECHNOLOGY (2010-11)

SUBMITTED BY

POOJA PANDEY

UNDER GUIDANCE OF

MRS. CHARU SHARMA

INDEX:-1) Definition and importance of chromosomal aberration.2) Variation in chromosome structure

a) Deletionb) Duplicationc) Translocationd) Inversion

3) variation inchromosome numbera) Euploidy

i. Monoploidy or haploidyii. Polyploidy Autopolyploids Allopolyploids Example-1)Raphanobrassica 2)evolution of wheat

b) Aneuploidy Hyperploidy Hypoploidy Trisomy Tetrasomy Monosomy nullisomyc) origin of aneuploids

4)genetic disorders

a) Down’s syndromeb) Turner syndromec) Klinefelter syndrome

CHROMOSOMAL ABERRATIONS

DEFINITION:-They are the visible changes in the structure of chromosomes, involving either in total number of genes loci in a chromosome or their rearrangement or change in the chromosome number. These are called as Chromosomal rearrangements or Chromosomal aberrations.

It is of 2 types:-1) Variation in chromosome structure2) Variation in chromosome number

Many chromosome mutation lead to abnormalities in cell and organisal function. There are 2 basic reasons for it :-1.Chromosomal mutation can result in abnormal gene number or position.2.If chromosome mutation includes chromosome breakage, then break may occur in middle of genes thereby distrupting its function.

Importance of chromosomal mutation:-1.In research, they provide ways of designing special arrangements of genes, uniquely suited to answer certain biological questions.2.they are important at applied level, especially in medicinal and in plant and animal breeding.

1) Variation in chromosome structure:-A) Changes involving the amount of DNA on a chromosomea. Deficiency or Deletion b. DuplicationB) Change in arrangement of gene locia. Translocationb. Inversion

VARIATION IN CHROMOSOME STRUCTUREIi is studied a lot from study of polytene chromosome-it is special kinds of chromosome found in certain tissue (such as salivary gland in larval stages of insects of order Diptera (Drosophila).

Polytene chromosome consists of chromatid bundles resulting from respected cycles of chromosome duplication with out nuclear or cell division, a process called as endoreduplication.

1)DEFICIENCY OR DELETION Definition:- The deficiency is the deletion of a chromosomal segment resulting in the loss of genes. Depending upon the length of the lost segment, the genes lost may vary from a single gene to a block containing several genes.

Nature:- The break in the chromosome may be induced by several agents such as chemicals, drugs and radiations. The break may occur at any time (spontaneous) during cell cycles either in somatic or germ cells. The breakage usually occurs at random and either in both the chromatids of a chromosome (chromosome break) or only in one chromatid (chromatid break). The loss of chromosomal segment occurs when a portion of chromosome gets detached due to certain reasons and the lost segment does not survive, because it lacks the centromere. The portion of the chromosomal carrying the centromere functions as a genetically deficient chromosome.

Types of deletion:-1) Terminal deletion:- It refers to the loss of a segment from one or the other end of

the chromosome. The terminal acentric part of the chromosome is unable to survive and causese terminal deletion. It is caused by a single break in the chromosome.

2) Intercalary or interstitial deletion:- It involves the loss of an intercalary segment of the chromosome with the reunion of terminal segments. Therefore, the intercalary deletion is caused by two breaks and reunion of terminal parts.

Although, deficiency and deletion are synonymous, but a distinction is often made. The loss of terminal segment of chromosomes is described as Deficiency, whereas the loss in intermediary position of chromosomes is designated by Deletion.

DETACTION OF DEFICIENCY:-1) By phenotypic effects shown in organisms having deleted chromosomes like notched

margin of wings in drosophila, therefore known as notch character.2) By cytological studies of homologously paired chromosome at meiotic prophase- The

normal chromosome when pairs with deletion chromosome during prophase of meiosis, its part homologous to deleted segment buckles out.

3) By cytological study of polytene chromosomes.

GENETIC PROPERTIES:-1) Failure of chromosome to survive as a homozygote; however this sffect could also be

produced by any lethal mutations.2) Chromosomes with deletion can never revert to a normal condition.

3) Criterion for inferring sometimes unmasks recessive alleles present on the other homolog leading to their unexpected expression this is called as Pseudodominance It is helpful in Deletion Mapping.

OCCURRENCE OF DEFICIENCY:-Deficiencies have been observed in both plants and animals. In Drosophila, a notch character is found, a number of deficiency characters are found in man, such as

a) Cri-du-Chat or cat cry syndrome caused by deletion in the short arm of chromosome 5.

b) Philadelphia chromosome caused in long arm of 22nd chromosome.

2)DUPLICATION

DEFINITION:- The presence of same block of genes more than once in a haploid complement is known as duplication and the additional block of genes is called a repeat.

TYPES OF DUPLICATION:-Three types of duplications have been recognized on basis of attachment of chromosme segment.1) Tandem duplication:- In tandem duplication the added segment has the same

genetic sequence as is present in the original state in the chromosome. Moreover the added segment lies in close association with original segment.

2) REVERSE TANDEM DUPLICATION: - In such a duplication the sequences of genes aligned in the attached chromosome piece is just the reverse of the original alignment.

3) DISPLACED DUPLICATION: - In it the chromosomal segment gets attached to some nonhomologous chromosome.

EXAMPLE:-An example f tandem duplication in Drosophila is the Bar character of the eye. Bar character is a dominant X linked character. It is controlled by 7 bands in 16A region of X chromosome. In normal female (heterozygous wild type) 16A region is represented once in both the X chromosome .In heterozygous double bar (BB/+) the 16A locus is represented three times in one X and only once in the other X chromosome . In homozygous ultrabar the 16A locus is represented three times in both the X chromosomes.

ORIGIN OF DUPLICATION:-Duplication can arise by any one of the 2 methods-a) By the attachment of a deleted from one chromosome to other.b) By unequal crossing over in the homologous chromosome.

SIGNIFICANCE:-They are more frequent and less deleterious. These do not lower the viability, but do produce abnormality of structure and function. Duplication play significant role in evolution , because dupli

cation increases number of genes in the chromosome complement. Duplications may overcome the effect of deletion, thus reducing their effect to nonlethal.

3)TRANSLOCATION

DEFINITION:-It is a chromosomal mutation in which there is a change in position of chromosome segments and the gene sequences they contain to a different location in the genome. No gain or loss of genetic material is involved in a translocation.

ORIGIN OF TRANSLOCATION:- Translocation occurs as a result of interchange of chromosome segments in nonhomologous chromosomes.

TYPES OF TRANSLOCATION:- Depending upon which part or parts of nonhomologus chromosomes become detached and reunited the translocation can be:-

a)SIMPLE TRANSLOCATION:-In such cases a small segment of a chromosome is added to the end of other nonhomologous chromosomes. This type of translocation is very

rare in nature and is caused by a single break in nature and is caused by a single break in one chromosome only.b)SHIFT TRANSLOCATION:-In it an interstitial segment of one chromosome is broker off and is inserted within the break in another nonhomologous chromosome. Thus it involves 3 breaks: two in one chromosome and one in nonhomologous chromosome.c)RECIPROCAL TRANSLOCATION:-It is the exchange of parts between nonhomologous chromosome. It is of 2 types:-

i. HOMOZYGOUS RECIPROCAL:-In which both the homologous chromosomes exchange parts with the 2 nonhomologous of another pair.

ii. HETEROZYGOUS TRANSLOCATION:- In which only one number of each of the 2 homologous pairs exchange part.

d)MULTIPLE TRANSLOCATION:-In it more than two pairs of nonhomologous chromosomes exchange parts.

BEHAVIOUR OF TRANSLOCATION ZYGOTES:-

a) HOMOZYGOUS TRANSLOCATIONS:- They can not be identified cytologically because these form regular bivelents at pachytene stage during meiosis.b) In Reciprocal translocation heterozygote the 2 normal and 2 interchanged chromosomes pair to form a cross shaped configuration at pachytene of meiosis, whereas normal chromosomes forms a bivalent. The anaphasic movement of chromosomes towards the poles takes place in any one of the three different ways given below:-

i. ALTERNATE SEGREGATION:- The alternate chromosomes of the ring go to the same pole; the normal chromosomes on one pole and the translocation chromosomes on the other pole. Therefore, all the gametes receive full complement and are fully viable.

ii. ADJACENT-1-SEGREGATION:-In open ring configuration, if one normal and one translocated chromosome reach one pole and are translocated and one normal chromosome to the other pole, it is called adjacent-1-segregati

iii. ADJACENT-2-SEGREGATION:-In some open ring congiguration the 2 homologous chromosomes( one normal and other translocated )go to one pole and the other two homologous go to other pole. This is called adjacent-2-segregation.

OCCURRENCE OF TRANSLOCATION:-It played an important role in introduction of genetic polymorphism in the population and origin of new species. Translocation have been studied in Drosophila, Oenothera, Maize .In man translocation between 15 and 21 chromosomes results in 21 trisomy and causes Down’s Syndrome.

SIGNIFICANCE OF TRANSLOCATION:-1) Translocation may cause change in the morphology or appearance of chromosomes by centric fusion between two acrocentric chromosome segments. This may lead to the change in the number of chromosomes.2) Translocation introduce genetic polymorphism in the populations of a species and play a significant role in formation of new varieties and new species.

INVERSIONDEFINITION:- Sometimes the number of genes in a chromosome is changed but the sequence of genes is altered by the rotation of gene block within a chromosome by 180 degree.

TYPES OF INVERSION:- It is of 2 types:-

a) Paracentric inversion:- When both the breaks in the chromosome during inversion occur on the same side of the centromere, means do not involve the centromere the inversion is known as paracentric.

b) Pericentric inversion:- In pericentric inversion the inverted segmaent contains the centromere, i.e. it involves one break on either side of the centromere.

Inversion occurring in a single chromosome is called chromosomal, whereas

that occurring in both the members of a homologous pair is called allelosomal. Allelosomal inversions occurring in the homologous arms of the 2 chromosomes are called allelobranchial, but those occurring in nonhomologous chromosomes are called heterosomal.

BEHAVIOUR OF INVERTED CHROMOSOMES:- The chromosome of a pair having identical inversions undergo normal meiotic pairing and are distributed normally during meiosis (homozygous). Even when heterozygous, the inversion has no detectable phenotypic effect but at the time of gamete formation, the normal pairing is disrupted and abnormal cytological configurations are produced. The paracentric heterozygous inversion with one chismata in the region of inversion results in the formation of an acentric chromatid lacking centromere, and a dicentric chromatid connecting the two chromosomes. Thus at the end of meiosis there are 2 non-crossover chromatids, one acentric chromatid and one dicentric chromatid. Both chromatids are inviable, so only the noncrossover chromatids form the viable products of meiosis in paracentric inversions of heterozygotes.

Crossing over in a pericentric heterozygous inversions result in the formation of the chromosomes which have duplications for certain genes and deficiency for others. The gametes receiving chromosomes with deficiency are rarely viable. Therefore, the recombination is lowered down in the heterozygous inversions.

for example, a chromosome with median centromere (V-shaped), may change into a hook shaped or rod shaped form. Conversely, in pericentric inversion a hook shaped chromosome may change into V shaped chromosome.

CONSEQUENCES OF INVERSIONS:-Since the number of genes in an inverted chromosome remains the same, the effects of inversion are not so drastic as are the effects of deletion and duplication –

i. Effects of inversion on phenotype may be produced because of position effect. A gene in one location on a chromosome does not necessarily have the same action that it could have in another position.

ii. Inversions suppress crossing over and tend to retain the original combination of genes it help in preserving the superior arrangement of genes.

iii. If 2 groups of organisms are separated for a long period, they might accumulate so many inversions of different types that these may lead to the formation of new species by the splitting of parental stock.

SIGNIFICANCE OF INVERSION:-i. Inversions help in the origin of new species.ii. Inversions provide proof for occurrence of crossins over and support the vies that only 2

of the 4 chromatids crossover.iii. Inversions, similar to translocation , help in establishing species relation in Drosophila.iv. As a result of inversions chances of crossing over are reduced and, therefore, the

recombination of genetic loci is restricted.

VARIATION IN CHROMOSOME NUMBEREach species of animals or plants has a fixed number of chromosomes. These chromosomes are represented once in haploid gametes and spores and twice in diploid body cells. Sometimes due to misdivision numerical changes in the number of chromosomes may occur. These can occur spontanelously by certain external or internal factors or by radiations. The phenomenon of variations in the number of chromosomes is called heteroploidy. It is of 2 types a :-1) EUPLOIDY 2)ANEUPLOIDY

EUPLOIDYIn euploidy, an organism either loses a complete set of chromosomes or acquires one or more additional sets of chromosomes over and above the 2 sets of diploid complement. Therefore, euploidy can be 2 types: monoploidy (n) and polyploidy.

1) MONOPLOIDY AND HAPLOIDY :- Monoploids have only one set or single basic set of chromosome.

Monoploids is rarely seen in normally adult diploid organism because of the presence of recessive lethal mutations( which are usually counteracted by dominant alleles in heterozygous individuals) in the chromosomes of many diploid eukaryotic organisms, many monoploids probably not survive. HAPLOIDS have half the somatic chromosome number. In diploid organism monoploids and haploid are identical while in a tetra or hexaploid with 4n or 6n chromosomes the haploids will posses 2n or 3n chromosomes whereas its monoploid will posses only one set(n) of chromosomes. Haploids of polyploids are called euploids, while those of aneuploids are called aneuhaploids.

ORIGIN OF HAPLOIDS:-In honeybee (Hymenoptera) haploid males (drones) are found as a routine. These arise parthenogenetically from the unfertilized eggs of dploid organism. Similarily haploids may originate spontaneously in flowering plants dur to parthenogenetic development of unfertilized egg. Such haploids have been obtained in tomatoes and cotton. Haploids can be artificially induced by any one of the following methods:-

a) by X-ray treatmentb) by delayed pollinationc) by temperature shocksd) by colchicines treatmente) by culturing pollen graibsf) interspecific or intergeneric hybridization.

MORPHOLOGY OF HAPLOIDS:-Haploids are smaller in size in comparison to diploids. Their leaves, flowers, fruits and seeds are also comparatively small. These are also less resistant and comparatively weak.CYTOLOGY OF HAPLOIDS;-The haploids have just univalent without any homologues to pair. These univalent are distributed at random during anaphase 1 or meiosis producing monosomics. Thus haploids are sterile.

USES OF HAPLOIDS:- Haploids are used to study the role of individual chromosomes. Homozygous diploids are obtained from such haploids by doubling the chromosomes with colchicine treatment

POLYPLOIDYOrganisms with more than 2 sets of chromosomes are known as polyploids i.e. these possess one or more haploids sets of chromosomes in addition to the original diploid configuration. Individuals with three sets of chromosomes (with additional one set) are known as triploids(3n), those with four sets of chromosomes (with additional 2 sets) are

tetraploids (4n), those with 5 sets are pentaploids(5n), with six sets of chromosomes are hexaploids(6n) and so on. This phenomenon of change in the number of sets of the chromosome is known as polyploidy.

Polyploids may arise spontaneously or be induced experimentally. They often occur as a result of a breakdown of the spindle apparatus in one or more meiotic divisions or in mitotic divisions. Almost all plants and animals probably have some polyploidy tissues. For example, the endosperm of plants is triploid, the liver of mammals and perhaps often vertebrates is polyploidy, and the giant abdominal neuron of sea hare Aplysia has about 75000 copies of the genome. Plants that are completely polyploidy include wheat, which is hexaploid(6n) and strawberry, which is octaploid(8n). There are 2 general classes of polyploids: those with an even number of chromosomes sets and those with an odd number of sets. Polyploids with an even number of chromosome sets have a better chance of being at least partially fertile, because there is the potential for homologs to be segregated equally during meiosis. Polyploids with an odd number of chromosomes sets always have an unpaired chromosome for each chromosome type, so the probability of producing a balanced gamete is extremely low; such organisms usually are sterile or have an increased of abortion of zygotes. In humans , the most common type f polyploidy is triploidy and it is always lethal. Triploidy is seen in 15 to 20% of spontaneous abortions and about 1 in 10000 live births, but most affected infants die within 1 month. Polyploidy is less consequential to plants. One reason is that many plants undergo self fertilization , so if a plant is produced with an even polyploid number of chromosome sets it can still produce fertile gametes and reproduce. Depending upon the source of additional chromosome sets, the polyploids are of 2 types-autopolyploids and allopolyploids

1) AUTOPOLYPLOIDS:- In it the chromosome set or sets of the same species is added to its diploid genome. If a diploid cell has AA genome an autotriploid will have AAA and an autotetraploid AAAA.

• Origin of autopolyploids:- The autoploid could arise in any of the following ways:-

By the union of diploid gametes produced in absence of meiosis or due to abnormal meiosis (autotetraploid).’ By somatic doubling of the chromosomes in a diploid zygote de to abnormal mitosis-(autotetraploid).

By the union of a haploid gamete with the diploid gamete-autotriploid By fertilization of an egg with 2 sperms- autotriploid By a cross between a tetraploid and a diploid parent-autipentaploid They are relatively rare in nature. These can be produced artificially. Example of natural autoploids are doob grass(cynodon dactylon)- an autotriploid, rye(secale cereale)

an autotetraploid. They are induced by treatment of colchicines in banana, datura, potato, coffee etc.Characteristics of autoployploids:-They exhibit following characteristics-

The autopolyploids are larger than the diploids due to increased cell size. Their leaves, flowers, fruits and seeds all are large. These show vigorous growth. Flowering is delayed but flowers are comparatively large. Seeds are few but large. Growth rate is slow due to slow rate of cell division. With increase in cell size, water content is increased causing reduced osmotic pressure and loss of resistance against frost. Polyploids above tetraploid level produces abnormalities like wrinkled leaves, dwarfing or weakling. Autooctaploids or higher have very low survival value.

Cytological behaviour ofautopolyploids:-Autopolyploids possess more than 2 sets of homologous chromosomes . This leads to the formation of multivalents (trivalents, quardivalents etc). Meiosis in triploids and pentaploids is abnormal. The thirs homologue either fails to pair forming a univalent(1:1) or is randomly distributed to the gametes(2:1). The number of chromosomes in the gametes of triploid organism may form trisomics or tetrasomics.

2) ALLOPOLYPLOIDS:- Allopolyploids are formed by multiplication of chromosome sets of a hybrid of 2 diploid species. This termed was coined by G.Karpencheko in 1928. usually the hybrids between 2 species are sterile because unrelated chromosomes do not pair during meiosis. Very rarely both the sets of chromosomes of the hybrid enter into one gamete cell producing diploid gametes. Such diploid gametes on fertilization produce allotetraploids. In some cases the diploid cell of the hybrid , on the onset of mitotic division undergoes chromosomes doubling but does not divide. Such a cell is tetraploid if it happen in the zygote an allotetraploid organisms develop.

Example:-1)Raphanobrassica the first known tetraploid reported by Russian geneticist karpenchenko.

• It is hybrid of Raphanus sativus and Brassica oleracea, developed by the fertilization of diploid gametes of F1 hybrid.

• Both radish and cabbage are diploid each with 18 chromosomes. Their gametes have 9chromosomes.The union of these gametes produce F1 hybrid with 18 chromosomes.

• These hybrids are sterile because the chromosomes of radish did not pair with thechromosomes of cabbage. Sometimes viable pollen and ovules having 18 chromosomes (diploid gamete) were formed.

• The fusion of these diploid gametes produced a allotetraploid (4n=36, n=9) with 18 chromosomes of radish and 18 chromosomes of cabbage. Such tetraploids produce viable gametes with 9 chromosomes of radish and 9 chromosomes of cabbage.

•

2)EVOLUTION OF WHEAT:-The common cultivated wheat is also an allopolyploid. Three different chromosomes complement series are found in different species of wheat genera-Triticum. The series is represented by 3 groups:-

a) Einkorn wheat group is represented by 2n=14 (the primitive diploid species). These are Triticum monococcum and T.Aegilopoids. The wheat is not suitable to human consumption because the grain is tightly enclosed in the glumes.

T.aegilopoides * A.speltoides (wild einkorn) (goat grass) 2n=14 2n=14 AA ↓ BB

HYBRID ↓ (sterile)

AB ↓ Triticum diocoides(ABBB) (2N=28) ↓Evolved into Triticum dicoccum (A’A’B’B’)

b)Emmer wheat group includes 7 allotetraploid species with chromosome complement 2n=28. The 2 most important species of tetraploid wheat are Triticum dicoccum and T. durum. The emmer wheat has evolved through hybridization between einkorn wheat and a wild species Aegilops (goat grass).

c)vulgare wheat group consists of 5 species of allohaxaploid wheat(2n=42). Triticum dicoccum * Aegilops squarrosa ( Tetraploid wheat) (goat grass) 2n=28 2n=14 A’A’B’B’ ↓ DD Triploid hybrid A’B’D ↓alloploidy

Triticum aestivu (allohexaploid) A’A’B’B’DD

SIGNIGICANCE OF POLYPLOID:- Autopolyploidy not only increases the size and vigour of the plant but also changes the size of fruits and pollens. It increases the osmotic concentration. Vitamins, alkloids and sugar contents of beet are also found to be increased. Polyploids also lead to changes in the season of blooming and fruiting and changes the annual plants into perennial plants. Thus autopolyploidy provides a method by which a type may become adapted to new and specially to less favourable conditions.

The allopolyploids suggest how new species would have arisen by crosses between 2 species. Polyploids can be used in propogating crops which are valued for vegetative organs. New varieties of plants for the improvement of crops in terms of resistance to diseases, higher yield, better quality can be obtained by interbreeding and polyploidy.

OCCURANCE OF POLYPLOIDS:-The polyploids occur frequently in plants but rarely in animals, because the plants can propogate vegetatively through grafting , by making cutting and by rooting them. Thus the sterile triploid, pentaploids etc. are maintained from generation to generation. Animals usually reproduce sexually through gamete formation. The gamete formation is not normal in polyploids due to abnormal meiosis or failure of chromosome pairing. The polyploids can be maintained and are seen in animals which reproduce exclusively by diploid parthenogenesis.

ARTIFICIAL INDUCTION OF POLYPLOIDY:-A number of chemicals have been found to induce polyploidy in plants, the most efficient and widely used chemical being colchicine, it inhibits the formation of spindle fibres during mitosis but not the doubling of chromosome.Maize and some other plants respond to changes in the temperature. So when kept in high or low temperature inhibit spindle formation and thus tetraploid cells are formed.

ANEUPLOIDYAneuploidy is the addition or loss of one or more chromosomes to the complete diploid chromosome complement of an organism. The organism with such chromosome complement are known as aneuploids.Aneuploiy can be of 2 types1) Hyperploidy 2) Hypoploidy

1) HYPERPLOIDY:- It is the addition of one more chromosome to the diploid gamete of an organism. It may be called:-a) Trisomy:-(2n+1) when only one more chromosome is added to the diploid genome or b) Tetrasomy(2n+2) whem both the chromosomes of a homologous pair are added to the diploid genome.2)HYPOLPLOIDY :- It is the loss of one or more chromosomes from the diploid genome. It is known asa)Monosomy-(2n-1) when there loss of 1 chromosome from the complete diploid set and b)nullisomy(2n-2) when there is loss of both the chromosomes of a homologous pair.

TRISOMY:- Individuals having 1 chromosome extra in the haploid genome are called trisomics. Inthem 1 chromosome is represented 3 times. The extra chromosome may belong to any one of the chromosomes of a haploid set. Example- trisomic in man is called as Mongolism( down’s syndrome).

Production of trisomics:-i. Trisomics may develop spontaneously due to nondisjunction of chromosomes during meiosis at the time of gamete formation. This produces gametes with n+1 chromosomes.

ii. These may be produced by selfing triploidsiii. By crossing triploids females with diploids males

Significance of trisomy:- They are used for locating genes on specific chromosomes.

TETRASOMY:-In it individuals particular chromosome of haploid set is represented 4 times in a diploid chromosomal complement. The general chromosomal formula for tetrasomics is 2n+2.

MONOSOMY:-In it organism lack 1 chromosome(2n-1) if 1 more chromosome of some other pair is also lost then it is also called as double monosomics(2n-1-1)

Some monosomics lack 1 complete chromosome, they are genetically imbalanced and, therefore, they are either lethal of reduced viability. Monosomics can easily be produced in polyploids, because they possess more than 2 chromosomes of each type and loss of one or more chromosomes could easily be located. The number of possible monosomics is equal to the haploid chromosome number.

NULLISOMY:-It lack both the chromosomes of a homologous pair of chromosomes. This is represented by 2n-2.

Origin of aneuploids:- aneuploids could arise by nondisjunction occurring during first meiotic division. Translocation also lead to the formation of trisomics and monosomics.

GENETIC DISORDERSA. Down’s syndrome :-

trisomy 21, is achromosomal condition caused by the presence of all or part of an extra 21st chromosome. It is named after John Langdon Down, the British physician who described the syndrome in 1866. The condition was identified as a chromosome 21 trisomy by Jérôme Lejeune in 1959 Down syndrome in a fetus can be identified with amniocentesis (with risks of fetal injury and/or miscarriage) during pregnancy, or in a baby at birth.Down syndrome is a chromosomal condition characterized by the presence of an extra copy of genetic material on the 21st chromosome, either in whole (trisomy 21) or part (such as due totranslocations) Many of the common physical features of Down syndrome may also appear in people with a standard set of chromosomes, includingmicrogenia (an abnormally small chin) an unusually round face, macroglossia protrudingor oversized tongue), an almond shape to the eyes caused by an epicanthic fold of the eyelid, upslanting palpebral fissures (the separation between the upper and lower eyelids), shorter limbs, a single

transverse palmar crease (a single instead of a double crease across one or both palms), poor muscle tone, and a larger than normal space between the big and second toes. Health concerns for individuals with Down syndrome include a higher risk for congenital heart defects, gastroesophageal reflux disease, recurrent ear infections, obstructive sleep apnea, and thyroid dysfunctions.

Trisomy 21

Trisomy 21 (47,XX,+21) is caused by a meiotic nondisjunction event. With nondisjunction, agamete (i.e., a sperm or egg cell) is produced with an extra copy of chromosome 21; the gamete thus has 24 chromosomes. When combined with a

normal gamete from the other parent, theembryo now has 47 chromosomes, with three copies of chromosome 21. Trisomy 21 is the cause of approximately 95% of observed Down syndromes, with 88% coming from nondisjunction in the maternal gamete and 8% coming from nondisjunction in the paternal gamete

Mosaicism

Trisomy 21 is usually caused by nondisjunction in the gametes prior to conception, and all cells in the body are affected. However, when some of the cells in the body are normal and other cells have trisomy 21, it is called mosaic Down syndrome (46,XX/47,XX,+21). This can occur in one of two ways: a nondisjunction event during an early cell division in a normal embryo leads to a fraction of the cells with trisomy 21; or a Down syndrome embryo undergoes nondisjunction and some of the cells in the embryo revert to the normal chromosomal arrangement. There is considerable variability in the fraction of trisomy 21, both as a whole and among tissues. This is the cause of 1–2% of the observed Down syndromes.]

Robertsonian translocation

The extra chromosome 21 material that causes Down syndrome may be due to a Robertsonian translocation in the karyotype of one of the parents. In this case, the long arm of chromosome 21 is attached to another chromosome, often chromosome 14 [45,XX,der(14;21)(q10;q10)]. A person with such a translocation is phenotypically normal. During reproduction, normal disjunctions leading to gametes have a significant chance of creating a gamete with an extra chromosome 21, producing a child with Down syndrome. Translocation Down syndrome is often referred to as familial Down syndrome. It is the cause of 2–3% of observed cases of Down syndrome. It does not show the maternal age effect, and is just as likely to have come from fathers as mothers.

Duplication of a portion of chromosome 21

Rarely, a region of chromosome 21 will undergo a duplication event. This will lead to extra copies of some, but not all, of the genes on chromosome 21 (46,XX, dup(21q)). If the duplicated region has genes that are responsible for Down syndrome physical and mental characteristics, such individuals will show those characteristics. This cause is rare and no rate estimates are available.

2)TURNER’S SYNDROME:-The persons with Turner’s syndrome are phenotypic females but their interphase nucleus is without a barr body.These are sterile females with poorly developed ovaries and underdeveloped breasts. These exhibit webbed neck low set ears and broad chest. Their intelligence is also below average. In such women, instead of normal overies only ridges of whitish tissue are present which are known as “streak gonads”. Many scientists use the term “gonadial dysgenesis” to replace Turner’s syndrome. They have 45chromosomes instead of 46. since they possess no barr body, it means they possess only one X chromosome(XO). They are retarded physically as well as mentally. They average about 4ft 10inches .Cause

Risk factors for Turner syndrome are not well known. Genetic mosaicism (46XX/45XO) is most often implicated, alongside nondisjunction(45XO) and partial monosomy (46XX). Nondisjunctions increase with maternal age, such as for Down syndrome, but that effect is not clear for Turner syndrome. It is also unknown if there is a genetic predisposition present that causes the abnormality, though most researchers and doctors treating Turners women agree that this is highly unlikely. In 75% of cases inactivated X chromosome is paternal origin. There is currently no known cause for Turner syndrome, though there are several theories surrounding the subject. The only solid fact that is known today is that during conception part or all of the

second sex chromosome is not transferred to the fetus. In other words, these females do not have Barr bodies, which are those X chromosomes inactivated by the cell.

3)KLINEFELTER SYNDROME :- Klinefelter discovered some XXY individuals which are phenotypic males. These have poorly developed male sex organs. Their face and hair are somewhat feminine abd these have somewhat enlarged breasts . They are , therefore, sexually sterile. Such abnormal males exhibit klinefelter’s syndrome. They possess 47 chromosomes. From these observations, it appears that Y chromosomes possess some genes which promote the emergence of male characteristics and the X chromosome produces female charavters or inhibits male characteristics.

Cause

The extra X chromosome is retained because of a nondisjunction event during meiosis I(gametogenesis). Nondisjunction occurs with when homologous chromosomes, in the case the X and Y sex chromosomes, fail to separate, producing a sperm with an X and a Y chromosome. Fertilizing a normal (X) egg produces an XXY offspring. The XXY chromosome arrangement

is one of the most common genetic variations from the XY karyotype, occurring in about 1 in 500 live male births

Another mechanism for retaining the extra X chromosome is through a nondisjunction event duringmeiosis II in the female. Nondisjunction will occur when sister chromatids on the sex chromosome, in this case an X and an X, fail to separate. An XX egg is produced which, when fertilized with a Y sperm, yields XXY offspring.

In mammals with more than one X chromosome, the genes on all but one X chromosome are not expressed; this is known as X inactivation. This happens in XXY males as well as normal XX females.[16] However, in XXY males, a few genes located in the pseudoautosomal regions of their X chromosomes, have corresponding genes on their Y chromosome and are capable of being expressed These triploid genes in XXY males may be responsible for symptoms associated with Klinefelter syndrome.

Thus these are some examples of genetic diseases which are caused due to changes in variation in chromosome number and chromosome structure. The branch of genetics which deal with the inheritance of characters in man is termed as human genetics.

REFRENCES:-

1)A Text book of Genetics by Dr. Veer Bala Rastogi.

2)Genetics by Russel

3)An introduction to genetic analysis by Anthony J.F.Griffith

4)Principle of genetics by E.J.Gardner.

5)en.wikipedia.org/wiki/Down-syndrome.

6) en.wikipedia.org/wiki/turner syndrome

7) en.wikipedia.org/wiki/klinefelter syndrome.