Chapter 8. Variations in Chromosome Structure and Number 

homologous: same relation, position, or structure

cytogenics: study of normal and abnormal chromosomes and their behaviour

chromosomal mutation: variations from the normal wild type chromosome structure and number

  • mutations can arise spontaneously or be induced experimentally by radiation or certain chemicals

telomeres: sequences at the end of chromosomes

polytene chromosomes: special kind of chromosome found in cells of salivary glands of some insects

chromocenter: proteinaceous structure that joins polytene chromosomes tgt

acentric: without a centromere

dicentric: two centromeres

pseudodominance: unexpected appearance of the recessive phenotype due to the deletion of the dominant allele

tandem: one in front of the other

position effect: inversion or translocation can change position of gene in genome so that expression is altered

euchromatin: condensed during cell division but uncoiled during interphase

heterochromatin: stays condensed during interphase and transcriptionally inactive

euploids: cells/organisms with one complete set of chromosomes or exact multiple of complete sets

aneuploids: organisms with chromosome numbers that are not exact multiples of the haploid set of chromosomes

nondisjunction: failure of chromosomes to separate during meiosis

Variations in Chromosome Structure

polytene chromosomes

  • chromatin bundles resulting from repeated cycles of chromosome duplication without nuclear division
  • can be 1000 times thicker than normal meiotic chromosomes
  • study has contributed much to our knowledge of chromosomal structure
    • chromosomal abnormalities = easily seen under light microscope
  • polytene chromosomes = joined together at their centromeres by a proteinaceous structure called chromocenter

Types of mutations

deletions

  • chromosomal mutation in which part of a chromosome is missing
  • starts with chromosomal breakage
  • induced by
    • heat
    • ionizing radiation
    • viruses
    • chemicals
    • transposable elements
  • do not revert back to wildtype
  • individuals heterozygous for deletion may be normal, but if homolog contains deleterious recessive genes, consequences may be drastic
  • if deletion involves loss of centromere, it results in an acentric chromosome
    • acentric chromosomes are lost during meiosis
  • deletion of an entire chromosome is lethal
    • no living humans with entire autosomal chromosome missing
  • in some organisms, can be detected through karyotyping
    • heterozygotes will have mismatched homologous pair
    • during meiosis, unmatched DNA can be seen looping out during synapsis
  • pseudodominance can occur if dominant allele is deleted
  • deletions can be used to physically map genes to chromosomes
  • Deletion mapping is commonly done with Drosophila polytene chromosomes
    • used to construct a detailed map of Drosophila polytene chromosomes
  • if deletions = large, its likely they are lethal
Cri-du-chat
  • heterozygous for deletion of part of short arm of chromosome 5
  • their cries sound like the mew of a cat
  • affects 1/50000 live births
Prader-Willi syndrome
  • heterozygous for deletion on the long arm of chromosome 15
  • affects 1/10000-25000 (mostly males)
  • weak due to poor sucking reflex
  • 5-6 years old, patients = compulsive eaters
  • eventually develops obesity and other health related problems
  • left untreated, individuals can feed themselves to death
  • other symptoms
    • mental retardation

duplications

  • chromosomal mutation that results in a doubling of a segment of a chromosome
  • size of duplication varies considerably and may occur at different locations/tandem config
  • tandem duplications can be a reverse tandem duplication
  • terminal tandem duplications are duplicated segments located at the end of the chromosome

   

  • heterozygous duplications result in unpaired loops in prophase I and can be detected cytologically
  • duplicated genes can diverge and acquire new functions
  • multi-gene families come from duplication events and subsequent diversification
    • most genes belong to multigene families
    • ex. actins, globins, and collagens
    • members of a family may perform slightly diff functions
    • ex. in humans, there are 35 different collagen genes, each making diff structures such as bones, cartilage, tendons, and ligaments
ex. Bar eye mutant in Drosophila
  • results from duplicated region on the X chromosome
  • homozygous for Bar? less eye facets than normal eyes resulting in slit-like appearance rather than oval

inversions

  • chromosomal mutation that arises when a segment of a chromosome is excised and then reintegrated at an orientation 180 degrees from the original
  • no loss of genetic material
  • can be phenotypic effects resulting if breakpoints are within a gene or its regulatory region
  • homozygous inversions can be detected because the linkage arrangement of genes can be altered
    • ex. ABCDEFG → ADCBEFG
  • homozygous for inversion? meiosis is normal, no problems
  • heterozygous for inversion + no crossover in inverted region? meiosis is normal, no problems
  • heterozygous for inversion + crossover in inverted region? meiosis effed, big problems
Paracentric inversions + heterozygote with crossover?
  • homologous chromosomes try to pair up as best as they can, inversion loop forms
  • crossover within inversion loop forms dicentric bridge
    • results when two centromeres of resultant chromosome migrate to opposite poles during anaphase I
    • dicentric chromosome breaks apart
    • acentric chromosome is lost
    • after meiosis II, two of the gametes receive DNA with many missing genes, these gametes aren’t viable
    • viable progeny can only arise from gametes where the chromosomes did not involve a crossover in the inversion loop
    • for paracentric inversion heterozygotes, viable recombinants are reduced or totally suppressed
Pericentric inversions + heterozygote with crossover?
  • homologues also pair by forming inversion loops
  • results in two viable gametes with non-recombinant chromosomes and two recombinant gametes that are inviable with non-recombinant chromosomes
    • inviable ones resulting from deletion of some genes and the duplication of other genes
  • no dicentric bridge is formed
  • no acentric chromosomes formed
  • if there are two crossovers, all four resulting gametes are viable

translocation

  • chromosomal mutation in which there is a change in position of chromosomal segments to a different location in the genome
  • no genetic material gained or lost
Nonreciprocal intrachromosomal translocation
  • chromosomal segment changes position within same chromosome
Nonreciprocal interchromosomal translocation
  • chromosomal segment changes position from one chromosome to another
Reciprocal interchromosomal translocation
  • exchange of segments between two chromosomes

   

  • translocations typically affect the products of meiosis
  • in some cases, gametes are produced with either duplications or deletions and consequently are inviable
  • in other cases, duplications stemming from translocation can yield viable gametes such as in familial Down syndrome
  • in homozygotes for reciprocal translocation
    • meiosis = normal
    • crossovers do not produce abnormal chromatids
heterozygotic for reciprocal translocation
  • chromosomes pair up as best they can, which results in a cross-like configuration in prophase I
  • made of 4-paired up chromosomes, each partially homologous to the others
  • semi sterile, because only about half of the gametes produced are viable
    • many gametes with duplications/deletions = viable BUT resultant zygotes are not
    • in plants, pollen grains with deletions or duplications do not develop and are nonfunctional
  • segregation at anaphase I occurs in 3 possible ways

Alternate segregation:

  • alternate centromeres migrate to the same pole
    • ex. N1 and N2 to one pole, T1 and T2 to the other
  • no information is deleted/duplicated
  • viable gametes
  • half have two normal chromosomes
  • other half has two translocated chromosomes

Adjacent 1 segregation:

  • adjacent non-homologous centromeres migrate to same pole
    • ex. N1, T2 to one and N2, T1 to the other
  • both gametes contain deletions and duplications
  • usually inviable
  • occurs as frequently as alternate segregation

Adjacent 2 segregation:

  • adjacent non-homologous centromeres migrate to same pole
    • ex. N1, T1 to one pole, N2, T2 to the other
  • always occurs in inviable gametes

Chromosomal Mutations and Human Tumours

  • most human tumours have chromosomal mutations, translocations = most common
  • some tumours = associated with specific chromosomal mutation

Chronic myelogenous leukemia

  • cancer involving uncontrolled proliferation of myoblasts
  • stem cells of white blood cells
  • 90 percent CML patients have Philadelphia chromosome, a result from reciprocal translocation between csome 22 and 9
    • translocation converts proto-oncogene to oncogene
    • ABL gene on csome 22 becomes fused to BCR gene on csome 9
    • fusion protein causes cells to proliferate
    • Gleevec = recent drug targets the fusion protein and shows promise in treatment of this cancer

Burkitt Lymphoma

  • viral-induced tumour that affects B cells of immune system
  • common in Africa
  • 90 percent of tumours in this condition related to a reciprocal translocation between csome 8 and 14
    • brings MYC gene to regulatory region of an antibody gene, resulting in the overexpression of the MYC gene producing an oncogene

Position effect

  • inversions and translocations do not usually produce mutant phenotypes unless chromosomal breakpoints occur within a gene
    • usually limited to meiosis in heterozygotes
    • COULD change position of gene in genome so that the expression is altered
    • called position effect
  • can occur if gene is normally in euchromatin is moved to heterochromatin

ex. Aniridia

  • congenital eye condition char. by severe underdevelopment of iris
  • caused by lack of function of the PAX6 gene (necessary for eye development)
  • expression of PAX6 is suppressed by position effect resulting from translocation

ex. fragile sites

  • when human chromosomes develop narrowing or unstained areas
  • csomes can break at these sites, causing deletions
  • more than 40 fragile sites have been identified
ex. Fragile X syndrome
  • second leading genetic cause of mental retardation
  • occurs 1/1250 males
  • occurs 1/2500 females
  • inherited in Mendelian manner
  • However, only 80 percent males with this condition are mentally disabled
  • phenotypically normal males are called normal transmitting males and they can pass the condition to their daughters
  • add the rest of the info about fragile X cause wtf

Variations in Chromosome Number

  • euploids
  • aneuploids

Changes in one or a few chromosomes

  • generation of aneuploidy occurs when cells with abnormal numbers of chromosomes are generated from nondisjunction
  • in aneuploidy, cells have more or less chromosomes than normal
    • in animals, mostly lethal
    • in plants, more tolerant to aneuploidy
    • in diploids, 4 types
    • nullisomy: loss of one homologous chromosome pair (2N-2). results from nondisjunction for the same chromosome during meiosis in both parents
    • monosomy: loss of a single chromosome (2N-1)
      • produce N as well as N+1 gametes
    • trisomy: single extra chromosome (2N+1)
      • produce 4 types of gametes
    • tetrasomy: extra chromosome pair(2N+2)
    • can result in double monosomic and double tetrasomics
    • can cause serious problems during meiosis
    • in humans, autosomal monosomy is extremely rare
    • embryos do not develop significantly and are lost in early pregnancy
Trisomy 21
  • Down Syndrome occurs with a frequency of 3.5/1000
  • characteristics
    • low IQ
    • epicanthal folds
    • short broad hands
    • short stature
  • correlation with maternal age
  • nondisjunction increases with the length of time primary oocyte is in ovary
  • mothers over age 35 are encouraged to undergo amniocentesis/ chorionic villus sampling
    • amniocentesis: removing and testing a small sample of cells from amniotic fluid
    • chorionic villus sampling: taking cell sample from chorionic villi
  • there is very small correlation with paternal age if mother is over 35
  • can also be caused by Robertsonian translocation, known as Familial Down Syndrome involving 14-21
    • this produces 3 copies of long arm of chromosome 21
Trisomy 13
  • Pateau syndrome
  • occurs with a frequency of 2/10000 live births
  • characteristics
    • cleft lip and palate
    • small eyes
    • extra fingers
    • extra toes
    • mental and developmental disability
    • cardiac anomalies
  • Usually death occurs within 3 months
Trisomy 18
  • Edwards syndrome
  • occurs in 2.5/10000
  • reasons unknown: 80 percent patients = female
  • characteristics
    • small size at birth
    • multiple congenital malformations
    • clenched fists
    • elongated skull
    • low-set malformed ears
    • mental and developmental disability
  • 90 percent die within 6 months due to cardiac problems

Changes in Complete sets of Chronosomes

  • euploidy
    • monoploidy = one set of chromosomes
    • polyploidy = more than the normal set of chromosomes such as
    • triploidy (3N)
    • tetraploidy (4N)
    • lethal in most species, less consequential in plants
    • played important role in plant evolution
Monoploidy
  • results from unfertilized eggs
  • found in haploid organisms such as fungi and algae
  • rarely observed in adult diploids because of recessive lethal genes
  • normal part of life in male bees, wasps, and ants
  • can be useful for isolating mutants because there is only dose for each gene
Polyploidy
  • arises spontaneously or can be experimentally induced
  • it often occurs as a result in the breakdown of the spindle apparatus in meiosis or mitosis
  • almost all plants and animals have some polyploidy tissues including plant endosperm (triploid)
    • liver of mammals = polyploid
    • abdominal neuron of Aplysia has about 75000 copies of the genome\
  • ex. Wheat (6N)
  • ex. Strawberries (8N)
  • ex. North American sucker fish, salmon, some salamanders
  • Polyploids can either have an even number or odd number of chromosome sets
    • in an even number, there is a better chance of being partially fertile because homologs can pair up
    • in an odd number, sterility usually occurs as it is difficult for homologues to pair up and segregate
  • in triploids, the probability of producing a haploid gamete is (1/2)^n
    • where n = number of haploid chromosomes
    • triploidy is seen in 15-20 percent of spontaneous abortions and 1/10000 live births
    • triploidy is always fatal
  • tetraploidy in humans is seen in 5 percent of spontaneous abortions
Autoploidy
  • occurs when all sets of chromosomes originate in the same species
  • results from defects in meiosis
    • produces diploid/triploid
  • occurs in bananas which are triploid and seedless as the seeds aren’t fertile due to problems with meiosis
  • seedless fruit such as watermelon and grapes results from odd-number polyploidy
Allopolyploidy
  • occurs when all sets of chromosomes come from different, but usually related, species
  • results from interbreeding of two different species to produce a diploid with two different sets of chromosomes
  • cell usually sterile, sometimes each set of chromosomes doubles
    • cell contains diploid set of chromosomes from each parent, thus allowing pairing at meiosis
    • results in viable gametes
    • fusion of these gametes produces an allotetraploid
    • ex. allohexaploid with 42 chromosomes, derived from three distinct species each species with a diploid set of 14 chromosomes
    • many agricultural and horticultural plants = allopolyploids