Transcript The Chromosomal Basis of Inheritance

The Chromosomal
Basis of Inheritance
Chromosome Theory of Inheritance

Developed by Walter
Sutton & Theodor Boveri
in 1902

“Mendelian genes have
specific loci on
chromosomes, and it is
the chromosomes that
undergo segregation
and independent
assortment.”
Drosophila Melanogaster



Thomas Hunt Morgan, Columbia University
His experiments with fruit flies (D. melanogaster)
confirmed that Mendel’s “heritable factors” (
)
are located on chromosomes
Why fruit flies?



Quick-breeding (2 weeks)
Produce many offspring (hundreds!)
Have only 4 pairs of chromosomes
• 3 pairs of autosomes, 1 pair of sex chromosomes
Morgan’s Experiments

Wild Type vs. Mutant Phenotypes

Wild type:
• “normal” phenotype for a
character/trait
• Examples: red eyes
• Symbolized by w+ (example)

Mutant phenotype:
• traits that are alternative to the
wild type
• Example: white eyes
• Symbolized by w (example)

Note:
• Gene symbols are taken from the
first mutant discovered
• Wild-type is not always dominant
over mutant; it can be the other
way around!
Sex-Linked Genes





Genes located on a sex chromosome (X or Y in humans) are
called sex-linked genes
Morgan mated a white-eyed male with a red-eyed female
All F1 offspring had red eyes 
 Concluded that wild type (red eyes) is dominant
F2 generation was 75% red:25% white (classic ratio)… but whiteeye showed up in males ONLY
Morgan concluded that the gene for eye color is located only on
the X chromosome
 Since red is dominant (w+) over white (w), females would need 2
w+ alleles to have white eyes, while males would need only one
Linked Genes

Definition:


Genes located on the same chromosome that tend to be inherited
together in genetic crosses because they are part of a single
chromosome that is passed along as a unit.
Thomas Hunt Morgan’s example:
Wild Type

Body Color
b+ = gray
Wing Size
vg+ = normal
wings
Mutant
b = black
vg = vestigial
wings
Morgan observed that there were disproportionate numbers of wild-type
(gray-normal wings), and double mutant (black-vestigial wings) flies
among the offspring
• These were the phenotypes of the original parents
• This is because the genes for body color and wing size are located on the
same chromosome in fruit flies and are therefore usually inherited together
Genetic Recombination

Recombination of Unlinked Genes:


50% frequency of recombination is observed for any 2
genes that are located on different chromosomes
Basis for Recombination:
• Random alignment of homologous chromosomes during
metaphase I of meiosis

Parents: YyRr (yellow, round) and yyrr (green, wrinkled)
• Some offspring are (yellow, wrinkled) and (green,
round)…
• This is recombination! 
Genetic Recombination

Recombination of Linked Genes:
Linked genes do NOT assort independently
because they are located on the same
chromosome and tend to move together
through meiosis and fertilization
 But how does genetic recombination occur
at all then??

• Crossing over between homologous
chromosomes during prophase I of meiosis!
Genetic Maps



By studying recombination
data, it is possible to create
genetic maps
If two genes are far apart on a
chromosome there is a higher
probability that a crossover
event will separate them than
if the two genes are close
together
Linkage maps show the
sequence of genes along a
chromosome
Chromosomal Basis of Sex in
Humans
There are 2 varieties of sex chromosomes
in mammals: X and Y
 A person who inherits two X chromosomes
(one from each parent)  female
 A person who inherits one X chromosome
and one Y chromosome  male
 50/50 chance either way!

Sex-Linked Disorders in Humans
In addition to determining sex, sex
chromosomes contain many genes that
determine traits that are unrelated to sex
 Far more males have sex-linked genetic
disorders… XY vs. XX

A female must inherit the recessive allele (if
it is a recessive disorder) from BOTH
parents in order to exhibit it
 A male must only inherit the recessive allele
from one of his parents in order to exhibit it

Sex-Linked Disorders in Humans
Sex-Linked Disorders in Humans


Color blindness
Duchenne muscular dystrophy



1/3500 males in US
Progressive weakening of the muscles and loss of
coordination
Hemophilia:


Sex-linked recessive trait defined by the absence
of a certain protein required for blood clotting
Prolific in royal families of Europe (intermarriage)
Alterations of Chromosome Number

During meiosis, nondisjunction occasionally
occurs
The members of a pair of a homologous
chromosomes do not move apart properly
during meiosis I
OR
 Sister chromatids fail to separate during
meiosis II


The other chromosomes are usually
distributed normally
Alterations of Chromosome Number
Alterations of Chromosome Number



Aneuploidy:
 Abnormal chromosome number
 Occurs when a gamete with one more or one less
chromosome than normal unites with another, normal gamete
Trisomy:
 Chromosome is present in triplicate (instead of duplicate)
 2n + 1
Monosomy:
 Only one chromosome is present in each homologous pair
(instead of 2)
 2n - 1
Alterations of Chromosomal Structure

Breakage of a chromosome can lead to 4 types of changes
in chromosome structure:

Deletion:
• chromosomal fragment lacking a centromere is lost during cell
division

Duplication:
• chromosomal fragment joins its homologous chromosome
Alterations of Chromosomal Structure

Inversion:
• chromosomal fragment attaches to the original chromosome in
the reverse orientation

Translocation:
• chromosome fragment joins a nonhomologous chromosome
Human Disorders due to
Chromosomal Alterations

Down Syndrome

Trisomy 21
• 3 chromosomes for
chromosome 21


Results in mental
retardation, characteristic
facial features, heart
defects, etc.
1/700 children in US
Human Disorders Due to
Chromosomal Alterations

Klinefelter Syndrome





XXY
1/2000 births
Male sex organs, but testes
are small
Feminine body
characteristics
Turner Syndrome


XPhenotypically female, but
sex organs do not mature at
adolescence