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2. CHROMOSOMAL BASIS OF INHERITANCE DROSOPHILA AS A MATERIAL FOR EXPERIMENTAL GENETICS y y y y y y y y y Thomas hunt morgan (the father of experimental genetics) selected fruitfly (drosophila melanogaster) (the jackpot of genetics) as experimental material though it is small in size (2mm). Following advantages of drosophilaIts easily available hovering over ripe mango/banana fruits where it feeds over yeast cells present over the fruit surface. The flies can be reared inside bottles having yeast culture over medium containing cream of wheat, molasses and agar. A new generation can be raised within two weeks from single mating producing hundreds of individuals. The animals can be temporarily inactivated with ether and examined by hand lens / dissection microscope. Female is distinguishable from male by its larger size and ovipositor. The animals possess 4 pairs of chromosomes of different sizes, Y chromosome is hooked and easily distinguished. Polytene chromosomes occur in salivary glands of larva which can indicate any type of abnormality. MORGAN y y y y y y y y y y Thomas hunt Morgan, an American geneticist and Nobel prize winner 1933 s considered as father of experimental genetics for his work and discovery of linkage, crossing over, sex linkage, criss cross inheritance, linkage maps, mutability of genes. He is considered fly man of genetics. He wrote the book the theory of gene. He discovered the basis for variations due to sexual reproduction. In 1910 he discovered linkage and differentiated between linked and unlinked gene. Morgan and castle in 1911 proposed chromosome theory of linkage showing that genes are located in chromosomes and show linear order. The strength of linkage between genes increases with the decrease in distance between them. He proposed chaisma type hypothesis showing that chaismata causes crossing over. Morgan and Sturtevant (1911) found that frequency of crossing between two linked genes is directly proportional to the distance between the two. 1% recombination is considered equal to 1 centi morgan (cM) or 1 map unit. LINKAGE y y y y y y Linkage is the phenomenon of certain genes staying together during inheritance through generations without any change or separation due to their being present on the same chromosome. Linkage was first suggested by Sutton and boveri. (1902- 1903).also gave chromosomal theory of inheritance. In 1910 Morgan clearly proved and defined linkage on the basis of his breeding experiments in fruitfly drosophila melanogaster. In 1911, Morgan proposed chromosome theory of linkage. It states thatLinked genes occur on the same chromosome. They lie in a linear sequence in the chromosome. There is tendency to maintain the parental combinations of genes except for occasional cross over's. Chromosomal Basis of Inheritance 26 y Strength of the linkage between two genes is inversely proportional to the distance between the two i.e. two linked genes show higher frequency of crossing over if the distance between them is higher and lower frequency if the distance is small. LINKED GENES y y y These genes are placed very closely on the chromosome an do not show independent assortment at the time of gamete formation. They show dihybrid ratio of 3: 1. In dihybrid cross, they show test cross ratio of 1:1. UNLINKED GENES y y y These genes are located distantly and undergo assortment (segregation). Show dihybrid ratio of 9:3:3:1. Show test cross ratio of 1:1:1:1. LINKED GENES y y Are those genes which occur on the same chromosome while unlinked genes are the ones found on different chromosomes. Linked and unlinked genes can be easily known from breeding experiments. TYPES OF LINKAGE y y Complete linkage. Incomplete linkage. COMPLETE LINKAGE y y y y Morgan 1919. The genes located in the same chromosome do not separate and are inherited together over the generations due to absence of crossing over. Complete linkage allows the combination of parental traits to be inherited as such. It is rare but has been reported in male drosophila and some other heterogametic individuals. INCOMPLETE LINKAGE y y y Genes present in the same chromosomes have a tendency to separate due to crossing over and hence produce recombinant progeny besides the parental type. The number of recombinant individuals is usually less than the number expected in independent assortment. In independent assortment all the four types (two parental types and two recombinant types) are each 25%. In linkage each of two parental types is more than 25% while each of the recombinant types is less than 25%. KEY CONCEPTS x x x x x x A gene is a region of DNA within the chromosome. Each gene has a specific location on the chromosome. In humans, males have one X and one Y chromosome, and females have two X chromosomes. A specific gene on the Y chromosome is required for human embryos to develop as males. Unless they are located far from each other, genes on the same chromosome tend to be inherited together, or linked. Genes on different chromosomes are not linked. Homologous chromosomes that pair during meiosis can exchange genes in a process called crossing-over. Chromosomal Basis of Inheritance 27 x x x The genotypes of offspring can be different from that of either parent as a result of crossing-over, the random distribution of maternal and paternal chromosomes into gametes, and fertilization. Many inherited genetic disorders in humans are caused by mutations of single genes. A far smaller number of human genetic disorders are caused by abnormalities in chromosome number or structure. THE ROLE OF CHROMOSOMES IN INHERITANCE x x x x x x x Mendel did not know what the physical properties of his “particles” were when he proposed his laws of inheritance. August Weismann suggested that chromosomes (discovered in 1882) were the location of hereditary material. Genes are located on chromosomes The idea that genes are located on chromosomes is known as the chromosome theory of inheritance. Chromosomes are composed of a single DNA molecule and many proteins. The physical location of a gene on a chromosome is called a locus. Chromosomes that pair during meiosis and contain the same gene loci and structure are called homologous chromosomes AUTOSOMES AND SEX CHROMOSOMES x x x x x x x Chromosomes that determine gender are called sex chromosomes; all other chromosomes are called autosomes. Autosomes are homologous pairs. Sex chromosomes can be homologous or non-homologous pairs Sex determination in humans Human females have two X chromosomes, and all their gametes contain one X chromosome. Human males have one X and one Y chromosome; half their gametes contain an X chromosome, and the other half contain a Y chromosome. The chromosome carried by the sperm determines sex in humans. LINKAGE AND CROSSING-OVER x x Exceptions to the law of independent assortment Thomas Hunt Morgan discovered some genes that were inherited together in his research on fruit flies Chromosomal Basis of Inheritance 28 x Genes that are located on the same chromosome and do not assort independently are said to be genetically linked WHAT IS LINKAGE? x x x x x Linkage is defined genetically: the failure of two genes to assort independently. Linkage occurs when two genes are close to each other on the same chromosome. However, two genes on the same chromosome are called syntenic Linked genes are syntenic, but syntenic genes are not always linked. Genes far apart on the same chromosome assort independently: they are not linked. Linkage is based on the frequency of crossing over between the two genes. Crossing over occurs in prophase of meiosis 1, where homologous chromosomes break at identical locations and rejoin with each other. LINKAGE AND CROSSING-OVER x x x x x x x Crossing-over disrupts genetic linkage If the linkage between two genes on a chromosome were complete, all offspring would be of a parental type. Morgan’s experiments showed that complete linkage was not occurring as a result of the presence of nonparental genotypes To explain the appearance of nonparental genotypes in linked genes, Morgan proposed that genes are physically exchanged between homologous chromosomes during meiosis. The exchange of genes between homologous chromosomes is called “crossing-over” Genes that are far from each other on a chromosome are more likely to be separated by crossingover than are genes that are close to each other. Genes that are very distant from one another on a chromosome will assort independently. CROSSING OVER x Chromosomal crossover (or crossing over) is an exchange of genetic material between homologous chromosomes. It is one of the final phases of genetic recombination, which occurs during prophase I of meiosis (pachytene) in a process called synapsis. Chromosomal Basis of Inheritance 29 HISTORY x x x x x Crossing over was described, in theory, by Thomas Hunt Morgan. He relied on the discovery of the Belgian Professor Frans Alfons Janssens of the University of Leuven who described the phenomenon in 1909 and had called it 'chiasmatypie'. The term chiasma is linked if not identical to chromosomal crossover. Morgan immediately saw the great importance of Janssens' cytological interpretation of chiasmata to the experimental results of his research on the heredity of Drosophila. Janssens 1909 was the first person to discover chaisma formation and related process of crossing over. Morgan 1910 found phenomena of linkage and recombination. The recombination or new recombination of genes is possible only due to exchange of genetic material between homologous chromosomes. Linkage is incomplete in such cases. PROCESS x x x x x x In a non-dividing cell, chromosomes are not visible by light microscopy, because chromatin spreads throughout the nucleus. During the metaphase of cell division, the chromatin condenses and becomes visible as chromosomes. At this time, each chromosome has been duplicated. A chromosome becomes two sister chromatids attached at the centromere. Chromosomes condense, and the spindle apparatus begins to form. However, after the chromosomes condense, the homologous chromosomes (each one itself a pair of sister chromatids) pair up with their homologues The resulting pair is called a tetrad, due to the fact that it has a total of four sister chromatids (two pairs of two) The chromosomes in a tetrad are bound side by side along their length by a protein apparatus called the synaptonemal complex. The chromosomes are perfectly lined up with each other, such that analogous genes are side by side. Chromosomal Basis of Inheritance 30 DYAD AND TETRAD x x x The familiar pattern of a two-chromatid chromosome (seen during mitosis) is called a dyad. During mitosis dyads line up at the metaphase plate and the division of the dyad (chromosome) during anaphase "creates" the new chromosomes. When the two homologous pairs are aligned (side by side) we call the pair a tetrad. Therefore, a tetrad is composed of two chromosomes - one maternal (M) and one paternal (P). A tetrad will have two centromeres and four chromatids (because it is made from two chromosomes). A dyad was a single (X-shaped) chromosome so a tetrad is composed of two dyads. MECHANISM OF CROSSING OVER x x The process of crossing over occurs by a mechanism called breakage and reunion theory of Darlington. It comprises four steps: synapsis, tetrad formation, exchange of chromatids and disjunction. SYNAPSIS x x x x The homologous chromosomes come to lie close together in pairs in the zygotene substage of the prophase of meiosis -1. Their pairing is called synapsis. The paired homologus chromosomes are called bivalents. Their chromatids are not visible at this stage. TETRAD FORMATION x x x The chromatids of each synapsed chromosome slightly separate and become visible in the pachytene substage of the prophase of meiosis. A group of four homologous chromosomes chromatids is called is called a tetrad. Crossing over occurs in the four stranded or tetrad stage. Chromosomal Basis of Inheritance 31 CROSSING OVER x x x x Crossing over occurs in the pachytene substage. The adjacent non sister chromatids break at homologous sites, mutually exchange small corresponding segments and rejoin. The process leads to physical exchange of segments and is so exact that neither chromatid gains or looses any genes. It occurs with the help of enzymes endonuclease, exonuclease, recombinase. DISJUNCTION x After the completion of crossing over, the synaptic forces end and the homologous chromosomes move apart. x The sites where crossing over occurs are called chaismata. x Therefore the above explained mode of crossing over is called chaisma-type hypothesis. SEX DETERMINATION x In diploid organisms with separate sexes , a specific pair of chromosomes determine the sex of the individual. x They are called sex chromosomes or allosomes or heterosomes. x All other chromosomes are termed autosomal chromosomes. DISSIMILAR SEX CHROMOSOMES x Dissimilar sex chromosomes exhibit four conditions in animals x xx-xy- in mammals including man, and most insects , including fruitfly ,one sex chromosome is smaller than the other in males. a. The larger one is known as x chromosome and the smaller one is known as y chromosome. b. The similar and dissimilar sex chromosomes of females and males are described as homomorphic and heteromorphic respectively. X AND Y CHROMOSOMES x x x x The sex chromosomes (X and Y) have 2 regions each: homologous and non homologous or differential. The differential regions carry completely sex linked genes as they do not undergo crossing over. The homologous regions carry incompletely sex linked genes because they undergo crossing over. The genes present in the differential regions of the y chromosome are called holandric genes. Chromosomal Basis of Inheritance 32 PORTIONS OF CHROMOSOMES x x x Homologous portion is that in which there are genes having alleles in both Y and X sex chromosomes. The homologous portions are situated more in the central part of the sex chromosomes, near the centromere. Heterologous portion is that whose genes do not have correspondent alleles in the other sex chromosome. These genes are located more in the peripheral regions of the arms of the Y and X chromosomes. XX-XO x x In certain insects, such as cockroach and some roundworms , the y chromosomes is missing so that the male has only one sex chromosome. The condition in the male is XO (O means absence of one sex chromosome) and in the female it is XX. ZW-ZZ x x x In many vertebrates (fishes, reptiles, birds) and insects butterflies, moths. The female has heteromorphic sex chromosomes and the male has homomorphic sex chromosomes. These conditions are briefly indicated as ZW and ZZ respectively. These letters are used to avoid confusion with XX- XY condition. ZW- ZZ TYPE x x x x x The male has two homomorphic sex chromosomes (zz) and is homogametic, and the female has two heteromorphic sex chromosomes(zw) and is heterogametic. Thus there are two types of eggs: each with Z and with W, and only one type of sperms i.e. each with Z. Fertilization of an egg with Z chromosome by a sperm with Z chromosome gives a zygote with ZZ chromosomes. This zygote develops into a male. Fertilization of an egg with W chromosome by a sperm with Z chromosome yields a zygote with ZW chromosomes. This zygote produces a female. The offspring have a sex ratio of 1:1. ZO-ZZ x x x x In some butterflies and moths the W chromosomes is lacking, so that the condition in the female is ZO and that in the male is ZZ The female is heterogametic and produces two types of eggs: half with Z and half without Z chromosome. Male has homomorphic sex chromosomes and is homogametic. It forms only one kind of sperms, each with Z chromosome. On fertilization by a sperm with Z chromosome, the Z containing egg gives rise to a male offspring (zz) and the Z lacking egg produces a female offspring (zo). MECHANISM OF SEX DETERMINATION x The mechanism that fixes the sex of an individual as it begins life Is called sex determination. 1. genetic or chromosomal. 2. environmental or nongenetic. 3. nonchromosomal. Chromosomal Basis of Inheritance 33 CHROMOSOMAL SEX DETERMINATION x XX-XY-though dissimilar the x and y chromosomes synapse in meiosis ,segregate and pass into different gametes. x The eggs are all alike each with an x chromosome. x The female is homogametic. x The male is heterogametic as it produces two types of sperms. This condition is called male digamety. The Y containing sperms and the X containing sperms are respectively called androsperms and gynosperms. x The two are produced in equal proportion. INFLUENCE OF SEX CHROMOSOMES x Early embryo develops rudimentary undifferentiated gonads and reproductive tracts. The gonad rudiments can give rise to testes or ovaries. The sex determining gene of the Y chromosome makes the embryo develop into a male. This gene codes for a gene regulatory protein called testis determining factor (TDF), which makes the gonads differentiate into testes. x The testes then produce the hormone testosterone which induces the development of male reproductive tract. x The testes also produce an inhibitory substance that causes regression of the female tract. x If testes do not differentiate till the sixth week of embryonic life, the gonads differentiate into ovaries. x Thus female is a default sex. SRY (SEX-DETERMINING REGION Y) GENE x x x x Since its discovery, the importance of the SRY gene in sex determination has been extensively documented: Humans with one Y chromosome and multiple X chromosomes (XXY, XXXY etc.) are usually males. Individuals with a male phenotype and an XX (female) karyotype—XX male syndrome—have been observed; these males have the SRY gene in one or both X chromosomes, moved there by chromosomal translocation. (However, these males are infertile.) Similarly, there are females with an XXY or XY karyotype. These females have no SRY gene in their Y chromosome, or the SRY gene exists but is defective (mutated). PLANTS x x x The flowering plants are mostly bisexual and lack sex chromosomes. The unisexual flowering plants tend to have ZZ- ZO type of sex chromosomal mechanism for sex determination. The female plants are ZZ and male plants ZO. 1. SEX DETERMINATION IN DROSOPHILA x x x x Calvin bridges demonstrated that in drosophila sex determining factor is the ratio of number of X chromosomes to the set of autosomes. 1. Individuals having X/A ratio of 1.0 are females and fertile. Eg. 2A+ XX or 3A + XXX. 2. If X/A ratio exceeds 1.0 meta females are produced which are weak and infertile. (2A + XXX). 3. X/A ratio of 0.5 is necessary for male sex differentiation (2A + XY). 4. When X/A decreases below 0.5 (3A +XY ; X/A ratio = 0.33) infertile metamales are produced. These findings suggested that in drosophila male development factors are localized on autosomes. The X chromosomes perhaps carry some female determining genes. This mode of sex differentiation is known as genic balance theory of sex determination. Chromosomal Basis of Inheritance 34 2. TIME OF SEX DETERMINATION x x In the animals with two types of sperms , the sex of the offspring is determined at the time of fertilization by a chance event. It is determined by the kind of sperm that fuses with the egg. HAPLOID DIPLOID MECHANISM OF SEX DETERMINATION x x x x x x Hymenopterous insects, such as bees, wasps saw flies and ants: an unfertilized egg develops into a male and a fertilized egg develops into a female. Female is diploid (2n), and the male is haploid (n). Eggs are formed by meiosis and sperms by mitosis. Fertilization restores the diploid number of chromosomes in the zygote which gives rise to the female. If the egg is not fertilized, it will develop but into a male. Thus sex is determined by the number of chromosomes. HONEY BEE x x x x x x x x Male honey bee has 16 chromosomes, undergoes mitosis and forms sperms. Female honey bee has 32 chromosomes has meiosis and makes eggs with 16 chromosomes each. If the sperm and egg undergo fusion i.e. fertilization they form female honey bee with 32 chromosome. If the egg with 16 chromosomes remains as such. It undergoes parthenogenesis and becomes male honey bee. In honey bee, the quality of food determines whether a diploid larva becomes a fertile queen or a sterile worker female. A larva fed on royal jelly, grows into queen. Thus the environment determines fertility or sterility of the bee but it does not alter the genetically determined sex. Queen is the ultimate controller???????? ROYAL JELLY Chromosomal Basis of Inheritance 35 TYPES OF BEES ENVIRONMENT x x x x x x x x x Chemical plays a unique role in the worm's sexual differentiation. Free-swimming Bonellia larvae are initially sexually undifferentiated. Larvae which land on unoccupied sea-floor mature, over the period of years, into adult females. Most larvae, however, come in contact with the bonellin in the skin of an adult female and are masculinised by this exposure. The chemical causes these larvae to develop into the tiny males, which cling to the female's body or are sucked inside it by the feeding tube, to spend the remainder of their lives inside her genital sac, producing sperm to fertilize her eggs, reliant on her for all other needs. The sex of a Green Spoonworm is thus determined by external, environmental factors (the presence or absence of bonellin), not by internal, genetic factors (chromosomes), as is the case with most other sexually-differentiated organisms. This environmental sex determination helps Green Spoonworm populations respond to the availability of burrows. In American alligator, snapping turtle and other reptiles sex is determined by environmental temperature. The temperature at which alligator eggs develop determines their sex. Chromosomal Basis of Inheritance 36 x x x x Those eggs which are hatched in temperatures ranging from 32 to 34 °C become males, while those in temperatures from 23 to 30 °C become female. Intermediate temperature ranges have proven to yield a mix of both male and females. The female will remain near the nest throughout the 65-day incubation period, protecting the nest from intruders. When the young begin to hatch they emit a high-pitched croaking noise, and the mother quickly digs them out. In turtles, a temperature below 28 °C produces more males, above 33 °C produces more females, and between 28 degree and 33°C produces male and female in equal proportion. MUTATION x x x The term mutation was introduced by Hugo de Vries in 1901. Mutation is defined as a rare, random, discontinuous, inheritable variation in the amount or the structure of the genetic material of a cell or organism. Mutation becomes part of the genotype of the cell. Mutations are caused by radiation, viruses, transposons and mutagenic chemicals, as well as errors that occur during meiosis or DNA replication TYPES OF MUTATIONS x x x x Mutations taking place in the germ cells are called germinal mutations. These are inherited by the next generation. Mutations appearing in the somatic cells are termed somatic mutations. They are inherited only by the daughter cells formed by mitosis from the mutant cells. TWO MAIN TYPES x x x x Chromosomal mutations Gene mutations The term mutation is usually restricted to alterations in the genes; the alterations in chromosomes are also inheritable variations and may be included In the term mutations. Chromosomal alterations are called chromosomal aberrations CHROMOSOMAL MUTATIONS OR ABBERATIONS x x x These mutations affect large portions of the chromosome and are observable under a microscope. They involve morphological modifications in chromosomes. They are of two types1. Intra-chromosomal modifications. 2. Inter-chromosomal modifications. INTRA-CHROMOSOMAL MODIFICATIONS x x These changes affect a single chromosome. They occur in two ways: deletion (deficiency) and inversion. In both cases, the process involves breakage and reunion of segments of chromosomes. Chromosomal Basis of Inheritance 37 DELETION (DEFECIENCY) x x A segment of a chromosome lacking a centromere separates and is lost x Deletion may be terminal or intercalaray (interstitial). x The affected chromosome loses certain genes, and becomes shorter than normal. x Deletion is noticeable at the time of synapsis of the homologous chromosomes. A segment of a longer chromosome remains unpaired in terminal deletion and forms a loop in intercalary deletion. DELETION INTRA CHROMOSOMAL EXAMPLE x x Cri du chat syndrome results by deletion of half of short arm of chromosome 5 in humans Cry of an infant having this disorder resembles the sound of a cat in pain; caused by abnormal larynx development INVERSION x x x A segment of a chromosome separates and rejoins it in an inverted position Inversion may also be terminal or intercalary. Intercalary inversion may be pericentric if the inverted segment includes the centromere in it, or paracentric if the inverted segment is on one side of the centromere Chromosomal Basis of Inheritance 38 INVERSION INTRA CHROMOSOMAL x x Deletions and inversions produce new locations for genes and may change phenotypic expression They may make affected chromosomes unable to pair in meiosis and sterility INTER-CHROMOSOMAL MODIFICATIONS x x x x These changes affect two chromosomes simulatneously. They also occur in two waysTranslocation Duplication TRANSLOCATION x x x x A segment of a chromosome breaks off and joins a non homologous chromosome Both the affected chromosome gets modified. The donor suffers deletion and becomes shorter than normal The recipient has an extra set of genes and becomes longer than normal This is simple or interstitial translocation RECIPROCAL TRANSLOCATION x x Two non homologous chromosomes mutually exchange segments The affected chromosomes retain their original size but have rearranged gene blocks Chromosomal Basis of Inheritance 39 x E.g.- Chronic Myeloid Leukemia (CML)- is caused by chromosomes 22 of malignant cells shortened through translocation of a segment of its long arm DUPLICATION x x It’s the occurrence of a chromosome segment more than once in a chromosome. Duplication may be in tandem sequence or reverse. Chromosomal Basis of Inheritance 40 EFFECT OF MORPHOLOGICAL CHROMOSOMAL ABERRATIONS x x The chromosomal mutations result in changes in the number of genes or in new positions on the genes in the chromosomes. This alters the base sequence of the DNA and hence genetic message sent to the mRNA. These changes if not lethal, may cause profound changes in the phenotype. x Inversion and translocation interfere in synapsis and reduce chances of crossing over. x CHROMOSOME NUMBERS x x x Any heritable change in the make up of an organism comes under the word mutation. The term also refers to the process by which such a change takes place Such changes under mutation include changes in chromosome either in numbers or in structure (chromosomal mutation). PLOIDY x x x x x Ploidy is the number of sets of chromosomes in a biological cell. Human sex cells (sperm and egg) have one complete set of chromosomes from the male or female parent. Sex cells, also called gametes, combine to produce somatic cells. Somatic cells therefore have twice as many chromosomes. The haploid number (n) is the number of chromosomes in a gamete. A somatic cell has twice that many chromosomes (2n). HETEROPLOIDY: VARIATION IN CHROMOSOME NUMBER x x x x Changes in chromosome number can occur by the addition of all or part of a chromosome (aneuploidy) The loss of an entire set of chromosomes (monoploidy) or the gain of one or more complete sets of chromosomes (euploidy). Each of these conditions is a variation on the normal diploid number of chromosomes and each of these can have drastic effects on phenotypic expression HETEROPLOIDY Aneuploidy - the abnormal condition were one or more chromosomes of a normal set of chromosomes are missing or present in more than their usual number of copies x Monoploidy - the loss of an entire set of chromosomes x Euploidy - an entire set of chromosomes is duplicated once or several times x Euploidy refers to cells with an exact multiple of the haploid number, N: x Diploid=twice the haploid number, 2N. x Triploid is 3x the haploid number, 3N. x Tetraploid=4x the haploid number, 4N, etc. x Aneuploidy are cells with an uneven number of chromosomes. x So, aneuploidy like trisomy 21 would be the same as diploid + 1 chromosome. Turner syndrome in humans is a case of aneuploidy because it's diploid - 1 or 45 chromosomes... EU=true, AN=not x x ANEUPLOIDY x x A normal chromosomal number is euploid Cells with extra or missing chromosomes are aneuploid Chromosomal Basis of Inheritance 41 x x Most autosomal aneuploids are spontaneously aborted Those that are born are more likely to have an extra chromosome (trisomy) rather than a missing one (monosomy) CONDITIONS OF ANEUPLOIDY x x x x x x Nullisomy: loss of both pairs of homologous chromosomes; individuals are called nullisomics and their chromosomal composition is 2N-2. Humans with this condition will not survive. Monosomy: the loss of a single chromosome; individuals are called monosomics and their chromosomal composition is 2N-1 Trisomy: the gain of an extra copy of a chromosome; individuals are called trisomics and their chromosomal composition is 2N+1 Tetrasomic: gain of an extra pair of homologous chromosomes; individuals are called tetrasomics and their chromosomal composition is 2N+2 In addition to these conditions, more than one pair of homologous chromosomes may be involved. For example, a double monosomic is missing one chromosome from each of two pair of homologous chromosome (designated 2N-1-1), and a double tetrasomic contains an extra pair of two pairs of homologous chromosomes (2N+2+2). NONDISJUNCTION- CAUSE OF ANEUPLOIDY x x x x The failure of chromosomes to separate normally during meiosis Produces gamete with an extra chromosome and another with one missing chromosome Nondisjunction during Meiosis I results in copies of both homologs in one gamete Nondisjunction during Meiosis II results in both sister chromatids in one gamete Chromosomal Basis of Inheritance 42 Chromosomal Basis of Inheritance 43 Chromosomal Basis of Inheritance 44 MONOSOMY x x Monosomy is a form of aneuploidy with the presence of only one chromosome (instead of the typical two in humans) from a pair. Partial monosomy occurs when only a portion of the chromosome has one copy, while the rest has two copies. HUMAN CONDITIONS DUE TO MONOSOMY x x x Turner syndrome - Women with Turner syndrome typically have one X chromosome instead of the usual two sex chromosomes. Turner syndrome is the only full monosomy that is seen in humans— all other cases of full monosomy are lethal and the individual will not survive development. Cri du chat syndrome -- (French for "cry of the cat" after the distinctive noise by affected persons' malformed larynx) a partial monosomy caused by a deletion of the end of the short p (from the word petit, French for small) arm of chromosome 5. 1p36 Deletion Syndrome - a partial monosomy caused by a deletion at the end of the short p arm of chromosome 1. MONOSOMY x x x x x x x Monosomy refers to lack of one chromosome of the normal complement. Monosomy of the sex chromosomes (45,X) causes Turner syndrome Turner's Syndrome: 2n-1. 45,X. 1/2000 females. 99% of affected fetuses die in utero Features include short stature, webbing at back of neck, incomplete sexual development (infertile), impaired hearing TURNERS TRISOMIES x x Most autosomal aneuploids cease developing as embryos or fetuses Most frequently seen trisomies in newborns are those of chromosomes 21, 18, and 13 - Carry fewer genes than other autosomes Chromosomal Basis of Inheritance 45 TRISOMY 21 x x x Down syndrome Most common trisomy among newborns Distinctive facial and physical problems Varying degrees of developmental disabilities Individuals more likely to develop leukemia Link with one form of Alzheimer disease TRISOMY 13 x x Patau syndrome Very rare and generally do not survive 6 months Serious mental and physical disabilities A distinctive feature: Eye fusion Chromosomal Basis of Inheritance 46 TRISOMY 18 x x Edwards syndrome Most due to non-disjunction in meiosis II in oocyte and do not survive Serious mental and physical disabilities A distinctive feature: Oddly-clenched fists KLINEFELTER SYNDROME x x x Called the XXY syndrome 1 in 500 male births Phenotypes include: - Incomplete sexual development - Rudimentary testes and prostate - Long limbs, large hands and feet - Some breast tissue development Chromosomal Basis of Inheritance 47 x Most common cause of male infertility KLINEFELTERS SYNDROME x x x Klinefelter syndrome, or XXY syndrome is a condition in which human males have an extra X chromosome. While females have an XX chromosomal makeup, and males an XY, affected individuals have at least two X chromosomes and at least one Y chromosome. Because of the extra chromosome, individuals with the condition are usually referred to as "XXY Males", or "47, XXY Males" TRIPLE X SYNDROME x Triple X syndrome is a form of chromosomal variation characterized by the presence of an extra X chromosome in each cell of a human female. Triple-X is a chromosomal condition which occurs only in females. A female affected by triple-X syndrome has an XX pair of chromosomes, as well as an additional chromosome, resulting in the formation of XXX AMNIOCENTESIS Detects about 1,000 of the more than 5,000 known chromosomal and biochemical problems Ultrasound is used to follow needle’s movement CHORIONIC VILLI SAMPLING Performed during 10-12th week of pregnancy Provides earlier results than amniocentesis However, it does not detect metabolic problems - And has greater risk of spontaneous abortion Chromosomal Basis of Inheritance 48 TETRASOMY x x A tetrasomy is a form of aneuploidy with the presence of four copies, instead of the normal two, of a particular chromosome. Cat eye syndrome where tetrasomy of chromosome 22 is present. SEX CHROMOSOMAL TETRASOMIES x x 48, XXXX syndrome 48, XXYY syndrome MONOPLOIDY x x x x x An individual that contains one half the normal number of chromosomes is a monoploid and exhibits monoploidy. Monoploids are very rare in nature because recessive lethal mutations become unmasked, and thus they die before they are detected These alleles normally are not a problem in diploids because their effects are masked by dominant alleles in the genome Some species such as bees, ants and male bees are normally monoploid because they develop from unfertilized eggs Consequently, these individuals will be sterile. Chromosomal Basis of Inheritance ..49.. EXERCISE – 1 1. In Down’s syndrome (Mongolism), the number of chromosomes in the somatic cells is (a) 45 (b) 47 (c) 23 – 1 (d) 21 – 1 11. Puffs in the salivary gland chromosomes represent the site of (a) Protein synthesis (b) RNA synthesis (c) DNA synthesis (d) Duplication of DNA 2. Hopoploidy resulting from the loss of a pair of chromosomes is called (a) Trisomy (b) Tetrasomy (c) Nullisomy (d) Monosomy 12. 3. A diploid plant for which monosomics have been isolated (a) Potato (b) Wheat (c) Tomato (d) Rice What are the chromosomes with more than two chromatids called ? (a) Lampbrush chromosomes (b) Polytene chromosomes (c) Aerocentric chromosomes (d) Allosomes 13. Which of the following is not a polytene chromosome ? (a) Salivary gland chromosome of fruit fly (b) Salivary gland chromosome of Cheironomous (c) Lampbrush chromosome of an amphibian oocyte (d) All of above 4. A chromosome with terminal centromere is known as (a) Acrocentric (b) Telocentric (c) Metacentric (d) Polycentric 5. The chromosome with median centromere and almost equal arms is called (a) Acrocentric (b) Metacentric (c) Submetacentric (d) Telocentric 14. The part of the chromosome which governs its movement is (a) Spindle fibres (b) Nucleosome (c) H1 protein (d) Kinetochore 6. Which shapes are assumed by acrocentric and telocentric chromosomes respectively at the anaphase of meiosis (a) I & V shape (b) V & J shape (c) J & I shape (d) I & J shape 15. Lamp brush chromosomes occur through (a) Diplotene of meiosis (b) Prophase of meiosis (c) Interphase (d) Metaphase of meiosis 7. The terminal end of a chromosome is called (a) Satellite (b) Metamere (c) Telomere (d) Centromere 16. Which of the following is a correct match ? (a) Down syndrome 21st chromosome (b) Sickel cell anaemia X-chromosome (c) Haemophilia Y-chromosome (d) Parkinson disease X & Y chromosome 17. Trisomy of 21st chromosome is called (a) Edward’s syndrome (b) Down’s syndrome (c) Patau’s syndrome (d) Cri-du-chat syndrome 18. Down’s syndrome is characterised by (a) 21 trisomy (b) Two X and one Y chromosome (c) 19 trisomy (d) Only one X chromosome 8. Which prevent the union of chromosomes (a) Centromeres (b) Kinetochores (c) Telomeres (d) Nucleolar organisers 9. What are the filaments constituting a chromosome called ? (a) Chromomere (b) Chromatin (c) Centromere (d) Chromonema 10. The chromosomes which remain condensed during interphase are known as (a) Polytene chromosomes (b) Heterochromosomes (c) Euchromosomes (d) Megachromosomes Chromosomal Basis of Inheritance ..50.. 19. The sub-units of chromatids are (a) Chromonemata (b) Chromosomes (c) Telomeres (d) Secondary constrictions 20. One function of the telomeres in a chromosome is to (a) ‘Seal’ the ends of the chromosomes (b) Start RNA synthesis (c) Identify the correct member of the homologous pair of chromosomes (d) Help two chromatids to move towards poles 21. The polytene chromosomes were discovered for the first time in (a) Drosophila (b) Musca domestica (c) Chironomus (d) Musca nebulo 27. Given below is a pedigree chart shwoing the inheritance of a certain sex-linked trait in humans The trait traced in the above pedigree chart is (a) dominant X-linked (b) recessive X-linked (c) dominant Y-linked (d) recessive Y-linked 22. Mutual exchange of chomosome segments between nonhomologous chromosomes is called (a) Deletion (b) Duplication (c) Inversion (d) Translocation 28. In a mutational event, when adenine is replaced by guanine, it is the case of (a) frameshift mutation (b) transcription (c) transition (d) transversion 23. Datura is a classical example of (a) Trisomy (b) (c) Monosomy (d) 29. The “cri-du-chat” syndrome is caused by change in chromosome structure involving (a) deletion (b) duplication (c) inversion (d) translocation 30. Given below is a pedigree chart of a family with five children. It shows the inheritance of attached earlobes as opposed to the free ones. The squares represent the male invididuals and circles the female individuals. Which one of the following conclusions drawn is correct ? 24. Triploidy Monoploidy A polyploid with genomes derived from same original species is (a) Amphidiploid (b) Allopolyploid (c) Autopolyploid (d) Autoallopolyploid 25. Genes located on Y-chromosomes are called (a) holandric genes (b) autosomal genes (c) sex-linked genes (d) mutant genes 26. Barr body represents (a) heterochromatin in male and female cells (b) all heterochromatin in female cells (c) Y-chromosomes in somatic cells (d) one of the two X-chromosomes in somatic cells of female (a) (b) (c) (d) Chromosomal Basis of Inheritance The parents are homozygous recessive The trait is Y-linked The parents are homozygous dominant The parents are heterozygous ..51.. 31. Given below is a representation of a kind of chromosomal mutation. What is the kind of mutation represented ? (a) (b) (c) (d) 32. 33. Deletion Duplication Inversion Reciprocal translocation Sickle cell anaemia has not been eliminated from the African population because (a) it is controlled by recessive genes (b) it is not a foetal disease (c) it provides immunity against malaria (d) it is controlled by dominant genes If a colourblind woman marries a normal visioned man, their sons will be (a) all normal visioned (b) one-half colourblind and one-half normal (c) three-fourths colourblind and none-fourth normal (d) all colourblind 34. The term ‘crossing over’ was introduced by (a) Morgan and Cattell (b) Sutton and Boveri (c) Bateson and Punnett (d) Beadle and Tatum 35. In human, sex linked trait is (a) Down’s syndrome (b) (c) Curly hair (d) Colour blindness Sickle cell anaemia 36. Sex determination by environmental factors is commony observed in (a) Drosophila melanogaster (b) Mirabilis jalapa (c) Melandrium album (d) Bonellia viridis 37. The absence of Y chromosome in human beings causes (a) Turner’s syndrome (b) Klinefelter’s syndrome (c) Down’s syndrome (d) No abnormality 38. A man with certain disease marries a normal woman. They have eight children (3 daughters and 5 sons). Al the daughters suffer from their father’s disease but none of the sons are affected. Which of the following mode of inheritance do you suggest for this disease ? (a) Sex limited recessive (b) Autosomal dominant (c) Sex linked dominant (d) Sex linked recessive 39. The first attempt to show linkage in plants was done in (a) Zen mays (b) Oenothera lamarckiana (c) Pisum sativum (d) Lathyrus odoratus 40. Different mutation referrable to the same locus of a chromosome give rise to (a) Multiple alleles (b) Pseudoalleles (c) Polygenes (d) Oncogenes 41. Which of the following is sex linked ineritance ? (a) Thalassemia (b) Phenylketonuria (c) Goitre (d) Haemophilia 42. Hypertrichosis or hairy ears is sex linked character associated with the (a) Y chromosome (b) X chromosome (c) XX chromosome (d) XY chromosome 43. People who carry an allele for normal haemoglobin and an allele for sickle cell are resistant to malaria they are example of (a) diploidy (b) outbreeding (c) heterozygotic advantage (d) recessive superiority 44. Criss cross inheritance means (a) X chromosome from female will pass to female of next-generation (b) X chromosome from a male will pass to a female of next generation (c) X chromosome from male will pass to a male of next generation (d) none of the above Chromosomal Basis of Inheritance ..52.. 45. In rabbit, two recessive genes produce a solid body colour and long hair in contrast to dominant spotted body colour and short hair. The result of a cross between heterozygous spotted short haired rabbit to salid long haired rabbit gives spotted, short haireed 48, spotted long haired 5, solid short haired 7, solid long haired 40, total 100. In terms of cross over units, how far are there two genes on the chromosome? (a) 40 map units (b) 7 units (c) 12 map units (d) 48 map units 46. Drosophila is used in genetic studies because (a) its chromosome complement is simple (b) a single mating produces over 100 off springs (c) life cycle time in small (10-20 days) (d) all of these 47. Baldness is more common in men than in women. It could be explained on the basis that (a) it is due to male hromone and genes are not involved (b) baldness genes are located on Y chromosome (c) genes of baldness are autosomal but influenced by androgens (d) genes of baldness are located on X chromosome only 48. One way of determine sex linked inheritance is (a) son resembles mother and daughter resembles father (b) both son and daughter resemble mother (c) both son and daughter resemble father (d) son resembles father and daughter resembles mother 49. A normal woman whose father was albino marries a man who is albino. What proportion of normal and albino can be expected among their offspring ? (a) All normal (b) All albino (c) 1 normal : 1 albino (d) 2 normal : 1 albino 50. Child has blood groups ‘O’ and his father is ‘B’ type. Then genotype of the father should be 0 0 B 0 (a) II (b) I I A B B B (c) I I (d) I I Chromosomal Basis of Inheritance 51. Usually the recessive character is expressed only when present in a double recessive condition. However single recessive gene can express itself in human beings when the gene is present on (a) the X chromosome of the female (b) the X chromosome of the male (c) any autosome (d) either an autosome or X chromosome 52. A man with type A blood married a woman who has type AB blood. we don’t known weather the man is homozygous or heterzygous for the I allele. Which one of the following types in the progeny of this couple would indicate that the man is heterozygous ? (a) O (b) A (c) B (d) AB 53. A colourblind girl is rare and can be born when (a) her father is colourblind and mother has normal vision but her mother’s father (maternal grandfather) is colourblind (b) her mother is colourblind, even if father has normal vision (c) even when both her parents have normal vision provided the grand parents were colourblind (d) her mother is colourblind and her father had normal vision but her paternal grandfather (father’s father was colourblind). 54. The example of sex linked trait in human being is (a) curly hair (b) colour blindness (c) sickle cell anaemia (d) all of these 55. The gene for haemophilia is located on chromosome of humans. It is normally impossible for a (a) haemophilic father to pass the gene to his son (b) carrier mother to pass the gene to her son (c) haemophilic father to pass the gene to his daughter (d) carrier mother to pass the gene to her daughter 56. One child is haemophilic (sex linked trait) while its fratermal twins brother is normal. Which one of the following information is most appropriate ? (a) Haemophilic child is male (b) The other child is female and the father is haemophilic (c) Child is monozygotic twin (d) The mother must have been heterozygous ..53.. 57. 58. 59. 60. The gene for brown eyes is dominant over the gene for blue eyes. Following are given some statements (i) For the child to be blue-eyed, at least one parent should be blue-eyed. (ii) Both parents with blue eyes will have a blue-eyed child (iii) Blue-eyed person will always show both the alleles different from brown-eyed person (iv) Identical twins of blue-eyed parents will both have either blue or brown eyes (v) For the child to be brown-eye one parent should be brown The correct statement are (a) (i), (iv) and (v) (b) (ii), (v) (c) (ii), (iii) (d) (i), (iii) Haemophilia is a X-linked disease. A haemophilic male marries a normal woman, whose father is also a haemophilic. It is expected that (a) half their children will be haemophilics (b) all the children will be haemophilics (c) one fourth of the children will be haemophilics (d) one of the children will be haemophilics Carrier of a genetic disorder (a) are indicated by solid symbols on a family pedigree (b) are involved in consanguineous mating (c) will produce children with the disease (d) are heterozygotes for the gene that can cause the disorder Sickle cell anaemia (i) follows the same inheritance pattern as that of haemophilia (ii) follows the same inheritance pattern as that of albinism (iii) is a sex linked trait (iv) is due to a single recessive point mutation leading to the substitution of a single amino acid in the E charn of haemoglobin of the sentences written above (a) all are correct (b) all but (i) are correct (c) all but (iii) are correct (d) (ii) and (iv) are correct 61. Match the columns : Column I Down’s syndrome Cri-du-chat syndrome Klinefelter’s syndrome Turner’s syndrome (a) (b) (c) (d) (a) (c) a-s, b-q, c-p, d-r a-s, b-q, c-q, d-r p. q. r. s. t. Column II An additional sex Loss of a part of chromosome 5 Absence of sex Presence of an extra chromosome Presence of two extra chromosome (b) (d) a-t, b-s, c-p, d-q a-s, b-q, c-r, d-p 62. Cat cry syndrome is due to nd (a) monosomy of 22 chromosome th (b) deletion in an arm of the 5 chromosome th (c) trisomy of 13 chromosome (d) monosomy of the sex chromosome 63. Tay Sach’s disease is (a) Recessive and autosomal (b) Dominant and autosomal (c) Sex-linked (d) No a hereditary disease 64. Number of barr bodies present in Turner’s syndrome is (a) 0 (b) 1 (c) 2 (d) 2 or 3 65. Sickle cell anaemia is (a) autosomal hereditary disease (b) allosomic hereditary disease (c) epistatic effect (d) nutritional disorder 66. Christmas disease is another name of (a) Sleeping sickness (b) Down’s syndrome (c) Haemophilia B (d) Hepatitis 67. Cri-du-chat is due to chromosomal aberration called (a) Duplication (b) Inversion (c) Deletion (d) Translocation 68. Which of the following chromosomal alterations does not alter genic balance but may alter phenotype because of differences in gene expression ? (a) Deletion (b) Inversion (c) Duplication (d) Nondisjunction Chromosomal Basis of Inheritance ..54.. 69. 70. 71. 72. 73. Drosophila flies with XXY genotype are females, but human beings with such genotype are abnormal males. It shows that (a) Y-chromOsome is essential for sex determination in Drosophila. (b) Y-chromosome is female determinant in Drosophila. (c) Y-chromosome is male determination in human beings. (d) Y-chromosome has no role in sex determination either in Drosophila or in human beings. The trait traced in the above pedigree chart is (a) dominant X-linked (b) recessive X-l inked (c) dominant Y-l inked (d) recessive Y-linked 74. Bird females have chromosome arrangement as (a) XY (b) XO (c) WZ (d) WW 75. The formation of multivalents at meiosis in diploid organism is due to (a) monosomy (b) deletion (c) inversion (d) reciprocal translocation 76. Colchicine prevents the mitosis of cells at which of the following stage? (a) Anaphase (b) Metaphase (c) Prophase (d) Interphase Which disease has XXY chromosome constitution ? (a) Down’s syndrome (b) Turner’s syndrome (c) Klinefelter’s syndrome (d) Okazaki syndrome 77. Genes of which one of the following is present exclusively on the X-chromosome in humans ? (a) Baldness (b) Red-green colour blindness (c) Facial hair/moustaches in males (d) Night blindness Barr-body in mammals represents (a) One of the two X chromosomes in somatic cells of females. (b) All heterochromatin of male & female cells. (c) Y chromosomes of male. (d) All heterochromatin of female cells 78. XO-chromosomal abnormality in human beings causes (a) Turner’s syndrome (b) Down’s syndrome (c) Klinefelter’s syndrome (d) none of the above 79. A normal woman whose father was colour blind, is married to a normal man. The sons would be (a) 75% colour blind (b) 50% colour blind (c) all normal (d) all colour blind 80. Mother and father both have blood group 4A’. They have two children one with blood group ‘O’ and second one with blood group ‘A’. They have (a) mother has homozygotic gene father has heterozygot I’A 1 A. (b) both are homozygotic (IAIA). (c) mother is heterozygotic (l Ai) and father is homozygotic (IAIA). (d) both are heterozygotic (IAi). XO chromosomal abnormality in humans causes (a) Turner’s syndrome (b) Down’s syndrome (c) Patau’s syndrome (d) Klinefelter’s syndrome Given below is a pedigree chart showing the in-heritance of a certain sex-linked trait in humans. Chromosomal Basis of Inheritance ..55.. 81. A person having 45 chromosomes and Y-chromosome absent, is suffering from : (a) Down's syndrome (b) Klinefelter's syndrome (c) Turner's syndrome (d) Gynandromorph 82. Monosomy and trisomy can be represented as: (a) 2n + l, 2n + 3 (b) 2n – l, 2n – 2 (c) 2n, 2n + 1 (d) 2n – l, 2n + l 83. A diseased man marries a normal woman and they get three daughters and five sons. All the daughters were diseased and sons were normal. The gene of this disease is : (a) sex-linked dominant (b) sex- linked recessive (c) sex-linked character (d) autosomal dominant 84. Haemophilic man marries a normal woman. Their offspring will be : (a) all boys haemophilic (b) all normal (c) all girls haemophilic (d) all haemophilic 85. Genetic identity of a human male is determined by (a) autosome (b) nucleolus (c) sex-chromosome (d) cell organelles 86. Father of human genetics is : (a) Bateson (b) (c) Mendel (d) Watson Archibald Garrod Chromosomal Basis of Inheritance ..56.. ANSWER KEY EXERCISE – 1 1. (b) 2. (c) 3. (c) 4. (b) 5. (b) 6. (c) 7. (c) 8. (c) 9. (d) 10. (b) 11. (b) 12. (b) 13. (c) 14. (d) 15. (a) 16. (a) 17. (b) 18. (a) 19. (a) 20. (a) 21. (c) 22. (d) 23. (a) 24. (c) 25. (a) 26. (d) 27. (a) 28. (c) 29. (a) 30. (d) 31. (c) 32. (c) 33. (d) 34. (d) 35. (b) 36. (d) 37. (a) 38. (c) 39. (d) 40. (a) 41. (d) 42. (a) 43. (c) 44. (b) 45. (c) 46. (d) 47. (c) 48. (a) 49. (c) 50. (b) 51. (b) 52. (c) 53. (a) 54. (b) 55. (a) 56. (d) 57. (b ) 58. (a) 59. (d) 60. (d) 61. (a) 62. (b) 63. (a) 64. (a) 65. (a) 66. (c) 67. (c) 68. (b) 69. (c) 70. (a) 71. (c) 72. (b) 73. (b) 74. (c) 75. (d) 76. (c) 77. (a) 78. (a) 79. (b) 80. (d) 81. (c) 82. (d) 83. (a) 84. (b) 85. (c) 86. (d) Dream on !! [\]^[\]^ Chromosomal Basis of Inheritance