Chromosome Genetics

Genetics of Chromosomes:
Introduction to Cytogenetics

In Principle:

Genes occupy physical locations (loci) in linear arrays on chromosomes
    Alterations in the number of chromosomes or relative order of genes affect expression

Chromosomes occur in species-specific sets (karyotypes)
    Chromosomes within sets have characteristic size & morphology
        [ Chromosomes, Chromatids, Arms, & C value]

Chromosome irregularities are associated with particular medical syndromes
       These are some of the most common classes of medical genetic disorders in humans

Chromosome morphology at the microscopic level

Chromosomes occur in sets: haploid number = n
    Eukaryotic chromosomes have arms (short p & long q) & a centromere (IG1 11.12,14)
        FN = # arms
        metacentric (q ~ p)
        acrocentric (q > p)
        telocentric (q >> p ~ 0 )
        Ex.: Karyotype of Homo sapiens: 2n = 46 = 44 + XX or 44 + XY
                   Metaphase karyotype has seven groups A - G (IG1 11.15smc, 11.15smc2)
                   autosomes vs sex chromosomes (XY system in mammals)
                 Alternative sex-determination systems (WZ) in birds (Aves)

       Cytological appearance of chromosomes
            euchromatin - non-staining [GC]-rich, genetically active
            heterochromatin - staining [AT]-rich, genetically inactive
Barr Body - an inactive X chromosome
                      dosage compensation between XX & XY karyotypes

         chromosome banding
              G-banding       - (G)iemsa bands = proteolytic enzyme treatment + Giemsa stain
                                     chromosome-specific banding patterns
                FISH banding - (fluorescent in situ hybridization) identifies translocations
                polytene chromosomes - endoreplication in Drosophila (2n = 8)

Variations in chromosome number
    Number of n sets: euploidy
        diploid number (2n) = two haploid sets
            haploid (monoploid) species: male bees & wasps Hymenoptera
            triploid (3n) - typically sterile (Ex.: seedless watermelon)
            polyploids
                autopolyploid - formed by duplication of set within species
                     tetraploid (4n) plants often larger than parents
                allopolyploid - formed by mating of different species: 2n x 2n = 4n'
                      Raphanobrassica = cabbage x radish hybrid
                      Xenopus frogs evolve by auto- & allopolyploidization: 2n = 20 ~ 108
                Triticum wheat is a diploidized hexaploid (6n)

    Number of chromosomes per set: aneuploidy
         Human cytogenetic disorders: 7.5% of spontaneous abortions
                                                           0.6% of live births

        monosomy: one chromosome missing - non-disjunction in meiosis
          X (XO) humans: Turner Syndrome ( 2n = 45, X)
            Y (YO) humans: fatal in utero
        trisomy: one chromosome duplicated (2n = 47, +21)
            XXX: standard female
            XXY: Klinefelter Syndrome ( 2n = 47, XXY )
            XYY: 'supermale' syndrome a misnomer
           Trisomy-21: Down Syndrome ( 2n = 47, +21 )
                most common, ~ 1 / 2000 live births
                Risk increase with later maternal age
          Rarer trisomies: Patau Syndrome    (Trisomy-13) ( 2n = 47, +13 )
                                    Edward Syndrome (Trisomy-18) ( 2n = 47, +18 )

Variations in chromosome arrangement
       Loss / duplication / transfer of partial chromosomes: segmental aneuploidy
             micro-deletion: small part of long arm of Chromosome 7 in Williams Syndrome (2n = 46, 7q11.23-)
             reciprocal translocations
                duplication / deletion gametes

heritable Down Syndrome
Philadelphia Chromosome (2n = 46, t 9q,22q)

Chronic Myologenous Leukemia (CML) [iGen3 16-12] (IG1 20.19)
             Unbalanced translocations:
   Cri-du-Chat Syndrome: loss of short arm of Chromosome 5 ( 2n = 46, 5p- )
      Rearrangements
             Synteny among species shows inter-specific evolution
             Robertsonian fusions / fissions: # arms constant, 2n # varies
                       Ex.: Homo has 2n = 46 vs Chimp, Gorilla, & Orangutan with 2n=48