Mutation

1
Mutation

• No genetics without variation
• Gene or point mutations (Chapter 7)
• an allelic change, a change at a single locus
• Chromosomal mutations (Chapter 13)
• segments, entire chromosomes or sets of
  chromosomes change
• aberrations due to changes in chromosome
  structure
• aberrations due to changes in chromosome number

2
Mutation

• Our order of discussion
• Discussion of chromosome structure (ch.12-13)
• human sex chromosome composition and X chromosome
  inactivation (pp. 431-2)
• anomalies due to changes in chromosome number
  (chapter 13)
• anomalies due to changes in chromosome structure
  (chapter 13)
• gene or point mutation (in conjunction with
  introduction to bacterial genetics chapter 7)

3
Peripheral WBCs must be stimulated by mitogen to
divide...
Colchicine increases number of cells in metaphase
(Causes microtubule depolymerization)
Hypotonic solution aids in spreading chromosomes
4
Karyotype analysis
5

• Centromere position
• metacentric chromosome arms equal in size
• acrocentric chromosome arms different sizes

NOR nucleolar organizing region site of
ribosomal RNA genes
Arrow marks secondary constriction (primary
constriction centromere)
6
Some human chromosomes have similar sizes and
shapes
To distinguish between them unambiguously
requires special staining techniques...
(pp. 422-23)
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8
Q
R
G
C
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10
Electron micrograph of G-banded metaphase
chromosome
11
Paris Conference (1971) reference bands p arm
short q arm long
300 bands at metaphase 1500 bands at
prometaphase
12

• Landmark bands divide arms into defined regions
• regions are numbered away from centromere
• individual bands within regions are numbered
  away from centromere

Telomeres specialized structures found at the
very end of linear chromosomes
13
X and Y Chromosomes Pair during Meiosis
14
Pairing occurs between pseudo- autosomal regions
of X and Y, where they share DNA homology
Y chromosome is relatively gene poor
Heterochromatin stains darkly, replicates later
in S phase, contains few genes Y heterochromatin
constitutive heterochromatin (always
genetically inactive)
15
Normal polymorphism (variation) in human Y
chromosomes
16
7th week
(Transcription factor)
Testes differentiation
Sox-9 ?
17
Males and females differ in the number of genes
present on the X chromosome

• Females have twice the number as males
• Is there a mechanism which compensates for this
  difference in X gene dosage between sexes?

18
Bertram and Barr 1948 Examination of interphase
nuclei in males and females
Barr Body
19
Barr Bodies in Individuals with Varying Numbers
of Sex Chromosomes
Number of Barr Bodies observed is one less than
the number of X chromosomes
20
Mary Lyon (early 1960s) Experiments with
sex-linked coat color genes in mice...
Female mice heterozygous for two different color
alleles show mosaicism for the allele
phenotypes...
The cytological and genetic observations were
integrated into a hypothesis that proposed X
inactivation as a means of genetic dosage
compensation
21
Early in embryogenesis, one of the two X
chromosomes of a female is randomly inactivated...
X1 inactivated
The cytological consequence of inactivation is
formation of a Barr body
All daughter cells produce clones containing the
same active X...
Mosaics are therefore produced...
22
Review of Lyon Hypothesis
23
Anhydrotic Dysplasia defect in sweat gland
distribution in epidermis...
grandmother
mother
Identical twins
24
Some Genes are Transmitted to the Embryo in an
Inactive Form in the Sperm and Egg Genomic
Imprinting

• In mammals, a small number of genes are passed
  on to the zygote in an inactive form embryos
  therefore inherit only one active gene
• some of these genes are inactivated in the egg
  some in the sperm
• if one parent passes a wild-type inactive gene
  and the other passes a mutation, individual will
  show mutant phenotype (Praeder-Willi maternal
  and Angelman Syndromes paternal)