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
Chromosome irregularities are
associated
with particular medical
syndromes
These are some of the major
classes of genetic disorders in humans
Chromosomes each comprise a single,
continuous
DNA molecule
DNA is systematically packaged into chromosomes
through several levels of coiling
Most DNA does not code for proteins
Non-coding
DNA occurs in several classes
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, geneticvally inactive
Barr Body - an inactive X chromosome
dosage compensation between XX & XY karyotypes
effect on semi-dominant X-linked expression:
the genetics of tortoiseshell
& calico cats
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) [iGen3 16.01]
Lampbrush chromosomes in Triturus salamanders (Amphibia)
Variations in chromosome number
Number of n sets: euploidy [iGen3 16-22]
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 polyploidization: 2n
= 20 ~ 108
Triticum wheat is a
diploidized hexaploid (6n)
Number of chromosomes per set: aneuploidy [iGen3 16-15]
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
[iGen3
16-16]
X 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 (misnomer)
Trisomy-21:
Down Syndrome ( 2n=47,
+21 ) [iGen3 16-17]
most
common,
~
1
/ 2000 live births
Associated with later maternal age
[iGen3 16-Table 02]
Rarer trisomies: Patau Syndrome (Trisomy-13) ( 2n=47, +13 ) [iGen3 16-20]
Edward Syndrome
(Trisomy-18)
( 2n=47, +18 ) [iGen3
16-18]
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-)
[HOMEWORK]
reciprocal
translocations ) [iGen3
16-11]
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-)
[iGen3 16-04]
Rearrangements
pericentric inversions include centromere [iGen3 16-09]
paracentric inversions occur within
one arm [iGen3
16-08]
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
Chromosome
architecture at the molecular level
OR: Whatcha gonna do
with all that junk inside your genes?
How is DNA packed into chromosomes?
1o coiling of
DNA helix
2o
coiling of DNA +
histone core = nucleosome
histone octamer:
(H2A, H2B, H3, H4) x 2
histone H1 + linker
DNA
3o coiling
of core + linker
forms Solenoid
six H1 subunits
4o
coiling of solenoid
loops to non-histone Scaffold
scaffold
supercoil chromatin thread
chromosome
Fine-scale DNA structure of
chromosomes [Chromosome 11
CSHL
Animation]
Protein-coding genes
have introns, exons,
promoters, enhancers
'exon shuffling' hypothesis
exons as protein domains
exon
recombination
occurs
via transposable elements
Human genomes include ~20,050
protein-coding "genes" in <5% of DNA
Telomeric DNA caps chromosomes (IG1 11.1
Research Briefing)
may limit lifespan of cells
in vitro and in vivo (aging) [Nobel Prize, 2009]
Repetitive DNA accounts
for >>50% of
human genome, within and
between coding
gene loci
Repeats may be dispersed or tandem
Tandem repeats - multiple copies arranged
end-to-end
satellite DNA - variable [G+C] content
NORs (nucleolus-organizer
regions) comprise multiple rDNA genes
5S, 18S & 28S rRNA gene clusters
multiple rDNAs allow
more efficient production of rRNA
VNTRs (variable number of tandem repeats)
micro- & minisatellites - 2 or 4~10bp repeats
Dispersed repeats
-
scattered
throughout
chromosome
set
SINEs (short interspersed
elements) may occur within
introns
Alu family
- 200 ~ 300 bp x
105s copies
Alphoid family - centromeric
heterochromatin, 170bp
x ~103 copies
LINEs (long interspersed
elements) occur between
genes
LI family - 6,400bp
x 10,000 copies
All text
material ©2012 by Steven M.
Carr