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
    Chromosomes within sets have  characteristic size & morphology
Chromosome irregularities are associated with particular medical syndromes
       These are some of the major classes of 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)
= # 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)
                  Chromosomes, Chromatids, Arms, & C value

       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  (IG1 11.Tab3)
                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)

                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 polyploidization: 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 
[iGen3 16-Table 01]

        monosomy: one chromosome missing -  non-disjunction in meiosis

            X (XO) humans: Turner Syndrome ( 2n = 45, X)
        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
: small part of long arm of Chromosome 7 in Williams Syndrome (2n=46, 7q11.23-) [HOMEWORK]
             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)
                  balanced translocations new species ?
             Unbalanced translocations:

Cri-du-Chat Syndrome: loss of short arm of Chromosome 5 ( 2n = 46, 5p- )
             pericentric inversions include centromere

             paracentric inversions occur within one arm
                   Inversion polymorphism  in Drosophila shows intra-specific evolution
             Synteny among species shows inter-specific evolution
             Robertsonian fusions / fissions: # arms constant, 2n # varies [centromeres]
                       Ex.: Homo has 2n = 46 vs Chimp, Gorilla, & Orangutan with  2n=48

All text material 2013 by Steven M. Carr