Chromosome Mutations: Variations in Chromosome Number and Arrangement PDF

Chromosome Mutations: Variations in Chromosome Number and Arrangement Chapter 6 1 Introduction Most members of diploid species normally contain precisely two haploid sets of chromosomes. Many known cases (chromosomal mutations or aberrations) vary from this pattern, which include – a change in the t...

Chromosome Mutations: Variations in Chromosome Number and Arrangement Chapter 6 1 Introduction Most members of diploid species normally contain precisely two haploid sets of chromosomes. Many known cases (chromosomal mutations or aberrations) vary from this pattern, which include – a change in the total number of chromosomes. – the deletion or duplication of genes or segments of a chromosome. – rearrangements of the genetic material within or among chromosomes. These changes can result in some form of phenotypic variation and may even be lethal. 2 3 Changes in Chromosome Number: Terminology Variations in chromosome number are known as aneuploidy when an organism gains or loses one or more chromosomes and has other than an exact multiple of the haploid set In euploidy, complete haploid sets of chromosomes are present. – Polyploidy occurs when more than two sets of chromosomes are present. 4 Chromosomal Disjunction Chromosomal variation can arise from nondisjunction, in which chromosomes or chromatids fail to disjoin and move to opposite poles during meiosis I or II, leading to a variety of conditions in humans and other organisms – Nondisjunction disrupts normal distribution of chromosomes into gametes. – Fertilization of abnormal gametes with normal gametes results in zygotes with three members (trisomy) or only one member (monosomy of this chromosome). 5 Figure 6-1 6 Monosomy The loss of one chromosome (2n – 1) may have severe phenotypic effects. Monosomy for the X chromosome occurs in humans (Turner syndrome) Monosomy for any of the autosomes is usually not tolerated in humans and other animals but better tolerated in the plant kingdom. – Death may occur due to lethals being unmasked, or a single recessive gene may be insufficient to provide life-sustaining function for the organism (haploinsufficiency). 7 Trisomy Trisomy (2n + 1 chromosomes) is usually more viable than the loss of a chromosome – Provided the chromosome is actually small Trisomies for autosomes have severe effects and are usually lethal during development. Trisomic plants are viable, but their phenotype may be altered. – Examples: Datura Rice – In both cases the larger the chromosome, the more the distinct the phenotype 8 Down Syndrome: Trisomy 21 Only human autosomal trisomy in which an individual would survive longer than 1 year past birth 1/800 live births Down syndrome has 12 to 14 characteristics, and affected individuals express 6 to 8 on average – Prominent epicanthic fold in each eye – Flat face, round head, short stature with protruding tongue – Short, broad hands with characteristic palm and fingerprint pattern – Mental retardation, average life span 50 years. Children are prone to respiratory disease and heart malformations. – Show a higher incidence of leukemia (20 times higher) Death in older individuals often due to Alzheimer’s disease, which usually occurs earlier than in normal population 9 Figure 6-2 10 Trisomy 21 A critical region of chromosome 21 contains the genes that are dosage sensitive in this trisomy and are responsible for many of the phenotypes – Down syndrome critical region (DSCR) An extra copy of the DSCR1 seems to be associated with decreased risk of some cancers. – Approximately 10% reduction – Gene product suppresses VEGF (vascular endothelial growth factor) VEGF promotes angiogenesis (formation of new blood vessels) Origin of Trisomy 21 Down syndrome most frequently occurs due to nondisjunction of chromosome 21 during anaphase I or II. – Seventy-five percent occur during Meiosis I. – Fertilization with a normal gamete creates the trisomic condition. Ninety-five percent of Down syndrome occurs from the egg carrying the extra chromosome 21. Increased incidence of Down syndrome with increasing maternal age. Female embryos’ oogonia are paused in meiosis I, and only proceed to meiosis II one at a time every month after puberty! – As a female ages the length of time the oogonia remain in meiosis becomes longer 12 Figure 6-3 13 Trisomy 21 Genetic counseling is recommended for women who become pregnant late in their reproductive years, and diagnostic testing may also be recommended. Diagnostic testing uses fetal cells obtained form amniotic fluid or placental chorion. – Amniocentesis – Chorionic villus sampling (CVS) Noninvasive prenatal genetic diagnosis (NIPGD) is a new approach to deriving cells from maternal circulation. Fetal cells are cultured, and the karyotype can be determined by cytogenetic analysis. 14 Other Human Aneuploidy In addition to Down syndrome only two other trisomies survive to term but manifest severe malformations and early lethality: – Patau syndrome Trisomy 13 80% die within first year of life – Edwards syndrome Trisomy 18 3% are born alive No autosomal monosomies survive to term! – n-1 gametes must be functionally impaired even though the frequency of them occurring is equal to n+1 gametes Karyotype analysis of spontaneously aborted fetuses reveal that at least 6 percent of all conceptions contain an abnormal chromosome complement. – Mostly Turner syndrome (45, X) But trisomies of every chromosome have been found 15 Polyploidy The naming of polyploids is based on the number of sets of chromosomes found: – – – – A triploid has 3n chromosomes. A tetraploid has 4n chromosomes. A pentaploid has 5n chromosomes. and so forth Polyploidy is relatively infrequent in many animal species but is well known in lizards, amphibians, and fish and is much more common in plant species – Uneven # of homologs not common to be seen in subsequent generations due to unbalanced gametes 16 Polyploidy: Autoploidy vs Alloploidy Polyploidy can originate by – the addition of one or more sets of chromosomes identical to the haploid complement of the same species (autopolyploidy) or – the combination of chromosome sets from different species as a consequence of interspecific matings (allopolyploidy) 17 Autopolyploidy Autopolyploids have additional sets of chromosomes; thus triploids are AAA, tetraploids are AAAA, and so on. Autotriploids usually arise spontaneously: – If a diploid gamete (due to nondisjunction of all chromosomes) is fertilized by a haploid gamete, – Or two haploid sperm cells fertilize a haploid ovum, – Or diploids crossed with tetraploids under experimental conditions can also give triploids. Triploids are characteristically sterile Because they have an even number, autotetraploids (4n) are theoretically more likely to be found in nature than autotriploids. Tetraploids arise when chromosomes have replicated and the parent cell fails to divide and instead enters interphase: the chromosome number will have duplicated (can happen spontaneously) – Experimentally done i) by applying heat or cold shock to diploid cells undergoing meiosis or ii) by applying colchicine to somatic cells undergoing mitosis 18 Figure 6-6 Note: Mitosis Colchicine interferes with spindle formation 19 Autopolypoidy Autopolyploids are larger, not due to an increase in number of cells, but from larger cells Autopolyploid flowers and fruits are often increased in size, making such varieties of greater or commercial value. – Some potato species, Winesap apples, commercial seedless bananas, seedless watermelon, and so on (triploids) – Propagated asexually Research has shown that as polyploidy increases, gene expression either increases or decreases at tenfold. – Two genes that encode G1 cyclins are repressed when ploidy increases. The polyploid cell stays in the G1 phase longer and grows to a larger size. 20 Allopolyploidy Arising from hybridization of two closely related species Chromosome sets are homeologous (partly homologous) If AA x BB gives AB progeny → then sterile – No synapsis Inability to produce viable gametes: a and b are non-homologous If AB undergoes genetic doubling, fertile AABB (allotetraploids) are produced with AB gametes – AABB, if the two species are known, we use amphidiploid 21 Variations in the Composition and Arrangement of Chromosomes There are two primary ways in which the structure of chromosomes can be altered – The total amount of genetic information in the chromosome can change. Deletions Duplications – The genetic material remains the same, but is rearranged. Inversions Translocations (reciprocal and nonreciprocal) 22 Figure 6-9 23 Variations in the Composition and Arrangement of Chromosomes In most instances, these structural changes are due to one or more breaks along the chromosomal axis followed by loss or rearrangement. – Breakages can occur spontaneously, or – Exposure to chemicals or radiation (X rays and gamma rays) can increase these breakages The ends produced by these break points are “sticky”, and so can rejoin other broken ends Alterations that occur in gametes are heritable. 24 Deletion When a chromosome breaks in one or more places and a portion of it is lost, the missing piece is referred to as a deletion (or a deficiency) – Example: Cri du Chat at chromosome 5 The deletion can occur – near one end (terminal deletion), or – from the interior of the chromosome (intercalary deletion) For synapsis to occur between a chromosome with a large intercalary deletion and a normal complete homolog, the unpaired region of the normal homolog must “buckle” out into a deletion or compensation loop 25 Duplication Duplications arise through unequal crossing over between synapsed chromosomes during meiosis or through a replication error prior to meiosis Duplication may result in – gene redundancy. – phenotypic variation. – genetic variability during evolution. 26 Duplication: Gene AmplificationRibosomal RNA Genes →gene redundancy Many gene products are not needed in every cell of an organism, while others are essential to all cells – rRNA is essential for protein synthesis – Multiple copies of genes code for rRNA (rDNA) – Gene amplification is a mechanism to increase the rDNA that codes for rRNA Not just for rRNA..others too especially in cancer 27 Duplication: The Bar Mutation in Drosophila → phenotypic variation Duplications result in Bar-eyed flies that have narrow, slit-like eyes versus normal ovalshaped eyes. – 16A region on the X chromosome responsible for eye shape is duplicated in Bar flies and triplicated in double Bar flies 28 Duplication: Its Role in Evolution Susumo Ohno (1970) suggested that gene duplication is essential to the origin of new genes during evolution. The duplicated copy can acquire many mutational changes over extended periods. – Over long evolutionary periods, the duplicated gene may change sufficiently so that its product assumes a divergent role in the cell. – The new function may impart an “adaptive” advantage to organisms, enhancing their fitness Support is provided by the discovery of genes that have a substantial amount of their organization and DNA sequence in common but whose gene products are distinct. – Trypsin and chymotrypsin, myoglobin and various forms of hemoglobin are so similar that members of each pair of genes probably arose from a common ancestor through gene duplication 29 Inversion An inversion involves a rearrangement of the linear gene sequence rather than the loss of genetic information In an inversion, a segment of a chromosome is turned around 180 within a chromosome An inversion requires two breaks in the chromosome and subsequent reinsertion of the inverted segment An inversion may arise from chromosomal looping The inverted segment may be long or short and may or may not include the centromere 30 Figure 6-14 A paracentric inversion does not include the centromere (this example). A pericentric inversion includes the centromere 31 Inversions Organisms with one inverted chromosome and one noninverted chromosome are called inversion heterozygotes. Synapsis of inverted chromosomes requires an inversion loop For a paracentric inversion crossover: – one recombinant chromatid is dicentric (two centromeres) with duplications and deletions – one is acentric (lacking a centromere) with duplications and deletions 32 Paracentric Inversion Effects of a single crossover within an inversion loop for paracentric inversion heterozygotes: – One recombinant chromatid is dicentric (not viable) – One recombinant chromatid is acentric (not viable) – One with a normal sequence (nonrecombinant) – One with an inverted sequence (nonrecomibnant) Pericentric inversion single crossovers: – Similar, but all have centromeres 33 Translocations Translocation is the movement of a chromosomal segment to a new location in the genome. A reciprocal translocation involves the exchange of segments between two nonhomologous chromosomes. – has an unusual synapsis configuration during meiosis – results in rearrangement of genetic material 34 Translocation Two possible segregation patterns: – one that leads to a normal and a balanced gamete (called alternate segregation) – one that leads to gametes containing duplications and deficiencies (called adjacent segregation) Only 50 % of the progeny survive → semisterility 35 Translocation: Familial Down Syndrome A Robertsonian translocation or centric fusion involves breaks at the extreme ends of the short arms of two acrocentric chromosomes. – The small segments are lost, and the larger segments fuse 36 Translocation: Familial Down Syndrome In familial Down syndrome, one of the parents contains a 14/21 translocation This individual is phenotypically normal but has only 45 chromosomes. – During meiosis, one-fourth of the gametes have two copies of chromosome 21: a normal chromosome and a second copy translocated to chromosome 14. – Fertilization by a standard haploid gamete results in an embryo with 46 chromosomes but three copies of chromosome 21, exhibiting Down syndrome. 37