Download THE CHROMOSOMAL BASIS OF INHERITANCE

THE CHROMOSOMAL BASIS OF
INHERITANCE
CHAPTER 15
Chromosome theory of inheritance:
• Genes have specific
locations (loci) on
chromosomes
• Chromosomes
segregate and assort
independently
Chromosomes tagged to reveal a specific gene (yellow).
Thomas Hunt Morgan – Columbia University
1910 | 1933
• Drosophila melanogaster – fruit fly
– 4 pairs of chromosomes
– Fast breeding: 2 week generations
– Sex chromosome: Females = XX Males = XY
• Sex-linked gene: located on X or Y chromosome
– Red-eyes = wild-type; white-eyes = mutant
– Specific gene carried on
specific chromosome
(only F2 males = mutant)
Classes of chromosomes
autosomal
chromosomes
sex
chromosomes
Sex determination
varies between
animals
Genes on sex chromosomes
• Y chromosome
– few genes other than SRY
• sex-determining region
• master regulator for maleness
• turns on genes for production of male hormones
– many effects = pleiotropy!
• X chromosome
– other genes/traits beyond sex determination
• mutations:
– Hemophilia
– Duchenne muscular dystrophy
– Color-blindness
Map of Human Y chromosome?
< 30 genes on
Y chromosome
Yellow = heterochromatin
Human development
•
•
•
•
Y chromosome required for development of testes
Embryo gonads indifferent at 2 months
SRY gene: sex-determining region of Y
Codes for protein that regulates other genes
Human X
chromosome
• Sex-linked
– usually means
“X-linked”
– more than
60 diseases traced
to genes on X
chromosome
Ichthyosis, X-linked
Placental steroid sulfatase deficiency
Kallmann syndrome
Chondrodysplasia punctata,
X-linked recessive
Duchenne muscular dystrophy
Becker muscular dystrophy
Chronic granulomatous disease
Retinitis pigmentosa-3
Norrie disease
Retinitis pigmentosa-2
Hypophosphatemia
Aicardi syndrome
Hypomagnesemia, X-linked
Ocular albinism
Retinoschisis
Adrenal hypoplasia
Glycerol kinase deficiency
Ornithine transcarbamylase
deficiency
Incontinentia pigmenti
Wiskott-Aldrich syndrome
Menkes syndrome
Androgen insensitivity
Sideroblastic anemia
Aarskog-Scott syndrome
PGK deficiency hemolytic anemia
Anhidrotic ectodermal dysplasia
Agammaglobulinemia
Kennedy disease
Pelizaeus-Merzbacher disease
Alport syndrome
Fabry disease
Immunodeficiency, X-linked,
with hyper IgM
Lymphoproliferative syndrome
Albinism-deafness syndrome
Fragile-X syndrome
Charcot-Marie-Tooth neuropathy
Choroideremia
Cleft palate, X-linked
Spastic paraplegia, X-linked,
uncomplicated
Deafness with stapes fixation
PRPS-related gout
Lowe syndrome
Lesch-Nyhan syndrome
HPRT-related gout
Hunter syndrome
Hemophilia B
Hemophilia A
G6PD deficiency: favism
Drug-sensitive anemia
Chronic hemolytic anemia
Manic-depressive illness, X-linked
Colorblindness, (several forms)
Dyskeratosis congenita
TKCR syndrome
Adrenoleukodystrophy
Adrenomyeloneuropathy
Emery-Dreifuss muscular dystrophy
Diabetes insipidus, renal
Myotubular myopathy, X-linked
Sex-linked genes
• Sex-linked gene on X or Y
• Females (XX), male (XY)
– Eggs = X, sperm = X or Y
• Fathers pass X-linked genes to daughters,
but not sons
• Males express recessive trait on the single X
(hemizygous)
• Females can be affected or carriers
Transmission of sex-linked recessive traits
Hemophilia
sex-linked recessive
H Xh x X
HY
HH
XHh
XH
female / eggs
male / sperm
XH
XH
Y
XH XH
XH Y
XH Xh
Xh
XH
Xh
XH Xh
XhY
carrier
disease
XHY
Y
Mendelian Inheritance in Humans
Pedigree: diagram that shows the relationship
between parents/offspring across 2+ generations
Woman =
Man =
Trait expressed:
Pedigree Analysis
X-inactivation
• Female mammals inherit 2 X chromosomes
– one X becomes inactivated during embryonic
development
• condenses into compact object = Barr body
• which X becomes Barr body is random
– patchwork trait = “mosaic”
XH 
XH X h
Xh
X-inactivation & tortoise shell cat
• 2 different cell lines in cat
Genetic Recombination: production of offspring
with new combo of genes from parents
• If offspring look like parents  parental types
• If different from parents  recombinants
• If results do not follow Mendel’s Law of Independent
Assortment, then the genes are probably linked
Linked genes: located on same chromosome and
tend to be inherited together during cell division
Crossing over: explains why some linked genes
get separated during meiosis
• the further apart 2 genes on same chromosome,
the higher the probability of crossing over and
the higher the recombination frequency
Calculating recombination frequency
Linkage Map: genetic map that is based on
% of cross-over events
• 1 map unit = 1% recombination frequency
• Express relative distances along chromosome
• 50% recombination = far apart on same chromosome
or on 2 different chromosomes
Exceptions to Mendelian
Inheritance
Genomic Imprinting
• Genomic imprinting: phenotypic effect of gene
depends on whether it came from the M or F parent
• Methylation: silence genes by adding methyl groups
to DNA
Non-Nuclear DNA
• Some genes located in
organelles
– Mitochondria, chloroplasts,
plastids
– Contain small circular DNA
• Mitochondria = maternal
inheritance (eggs)
Variegated (striped or spotted) leaves result from mutations in
pigment genes in plastids, which generally are inherited from
the maternal parent.
Genetic Testing
Reasons for Genetic Tests:
• Diagnostic testing (genetic disorders)
• Presymptomatic & predictive testing
• Carrier testing (before having children)
• Pharmacogenetics (medication & dosage)
• Prenatal testing
• Newborn screening
• Preimplantation testing (embryos)
Prenatal Testing
• May be used on a fetus to detect genetic
disorders
• Amniocentesis: remove amniotic fluid
around fetus to culture for karyotype
• Chorionic villus sampling: insert narrow tube
in cervix to extract sample of placenta with
fetal cells for karyotype
Nondisjunction: chromosomes fail to separate
properly in Meiosis I or Meiosis II
Karyotyping can detect nondisjunctions.
Down Syndrome = Trisomy 21
Nondisjunction
Klinefelter Syndrome: 47XYY, 47XXY
Nondisjunction
Turner Syndrome = 45XO
Nondisjunction
• Aneuploidy: incorrect # chromosomes
– Monosomy (1 copy) or Trisomy (3 copies)
• Polyploidy: 2+ complete sets of chromosomes;
3n or 4n
– Rare in animals, frequent in plants
A tetraploid mammal. Scientists think this species may have arisen when an
ancestor doubled its chromosome # by errors in mitosis or meiosis.
Chromosomal Mutations
Chromosomal Mutations