Chapter 15

The Chromosomal Basis

of Inheritance
 Timeline
• 1866- Mendel's Paper
• 1875- Mitosis worked out
• 1890's- Meiosis worked out
• 1902- Sutton, Boveri et. al. connect
chromosomes to Meiosis.
 Sutton
• Developed the “Chromosome Theory of
Inheritance”.
• Mendelian factors or alleles are located
on chromosomes.
• Chromosomes segregate and show
independent assortment.
 Morgan
• Chose to use fruit flies as a test organism in
genetics.
• Allowed the first tracing of traits to specific
chromosomes.
 Fruit Fly
• Drosophila melanogaster
• Early test organism for genetic studies.
 Reasons
• Small
• Cheap to house and feed
• Short generation time
• Many offspring
• Few chromosomes
 Genetic Symbols
• Mendel - use of uppercase or lowercase
letters.
T = tall
t = short
• Morgan: symbol from the mutant
phenotype.
+ = wild phenotype
 Examples

• Recessive mutation:
– w = white eyes
– w+ = red eyes
• Dominant Mutation
– Cy = Curly wings
– Cy+ = Normal wings
 Morgan Observed:
• A male fly with a mutation for white eyes.
 Morgan crossed
• The white eye male with a normal red eye
female.
 The F1 offspring:
• All had red eyes.
• This suggests that white eyes is a genetic
_________?
• Recessive.
 F1 X F1 = F2
• Morgan expected the F2 to have a 3:1
ratio of red:white
• He got this ratio, however, all of the
white eyed flies were MALE.
• Therefore, the eye color trait appeared to
be linked to sex.
 Morgan discovered:
• Sex linked traits.
• Genetic traits whose expression are
dependent on the sex of the individual.
Fruit Fly Chromosomes
 Morgan Discovered

• There are many genes, but only a few

chromosomes.
• Therefore, each chromosome must carry a
number of genes together as a “package”.
 Linked Genes
• Traits that are located on the same
chromosome.
• Result:
–Failure of Mendel's Law of
Independent Assortment.
–Ratios mimic monohybrid crosses.
 Body Color
and Wing type
 Example
b+b vg+vg X bb vgvg
(b+ linked to vg+)
(b linked to vg)
If unlinked: 1:1:1:1 ratio.
If linked: ratio will be altered.
 Crossing-Over
• Breaks up linkages and creates new ones.
• Recombinant offspring formed that doesn't
match the parental types.
 If Genes are Linked:
• Independent Assortment of traits fails.
• Linkage may be “strong” or “weak”.
 Linkage Strength
• Degree of strength related to how close the
traits are on the chromosome.
– Weak - farther apart
– Strong - closer together
 Genetic Maps
• Constructed from crossing-over
frequencies.
• 1 map unit = 1% recombination frequency.
• Comment - only good for genes that are
within 50 map units of each other. Why?
 Genetic Maps
• Have been constructed for many traits in fruit
flies, humans and other organisms.
 Sex Linkage in Biology
• Several systems are known:
1. Mammals – XY and XX
2. Diploid insects – X and XX
3. Birds – ZZ and ZW
4. Social insects – haploid and diploid
Chromosomal Basis of Sex in Humans
• X chromosome - medium sized chromosome
with a large number of traits.
• Y chromosome - much smaller chromosome
with only a few traits.
 Human Chromosome Sex
• Males - XY
Females - XX
• Comment - The X and Y chromosomes are a
homologous pair, but only for a small region at
one tip.
 SRY
• Sex-determining Region Y chromosome gene.
• If present - male
• If absent - female
• SRY codes for a cell surface receptor.
 Sex Linkage
• Inheritance of traits on the sex chromosomes.
• X- Linkage (common)
• Y- Linkage (very rare if exists at all)
 Males
• Hemizygous - 1 copy of X chromosome.
• Show ALL X traits (dominant or recessive).
• More likely to show X recessive gene
problems than females.
 X-linked Disorders
• Color blindness
• Duchenne's Muscular Dystrophy
• Hemophilia (types a and b)
• Immune system defects
Samples of X-linked patterns:
 X-linked Patterns
• Trait is usually passed from a carrier mother
to 1/2 of sons.
• Affected father has no affected children,
but passes the trait on to all daughters who
will be carriers for the trait.
 Comment
• Watch how questions with sex linkage are
phrased:
• Chance of children?
• Chance of males?
 Can Females be color-blind?
• Yes, if their mother was a carrier and their
father is affected.
 Y-linkage
• Hairy ear pinnae.
• Comment - new techniques have found a
number of Y-linked markers that can be
shown to run in the males of a family.
– Ex: Jewish priests
 Sex Limited Traits
• Traits that are only expressed in one sex.
• Ex – prostate
 Sex Influenced Traits
• Traits whose expression differs because of
the hormones of the sex.
• These are NOT on the sex chromosomes.
• Ex. – beards, mammary gland development,
baldness
 Baldness
• Testosterone – the trait acts as a
dominant.
• No testosterone – the trait acts as a
recessive.
• Males – have gene = bald
• Females – must be homozygous to have
thin hair.
 Barr Body
• Inactive X chromosome observed in the
nucleus.
• Way of determining genetic sex without doing
a karyotype.
 Lyon Hypothesis
• Which X inactivated is random.
• Inactivation happens early in embryo
development by adding methyl (CH3)
groups to the DNA.
• Result - body cells are a mosaic of X types.
 X Inactivation Examples
• Calico Cats.
• Human examples are known such as a
sweat gland disorder.
 Calico Cats
• XB = black fur
• XO = orange fur
• Calico is heterozygous, XB XO.
 Question?
• Why don’t you find many calico males?
• They must be XB XOY and are sterile.
 Chromosomal Alterations
• Changes in number.
• Changes in structure.
 Number Alterations
• Aneuploidy - too many or too few
chromosomes, but not a whole “set” change.
• Polyploidy - changes in whole “sets” of
chromosomes.
 Nondisjunction
• When chromosomes fail to separate during
meiosis
• Result – cells have too many or too few
chromosomes which is known as aneuploidy
 Meiosis I vs Meiosis II
• Meiosis I – all 4 cells are abnormal
• Meiosis II – only 2 cells are abnormal
 Aneuploidy
• Caused by nondisjunction, the failure of a pair
of chromosomes to separate during meiosis.
 Types
• Monosomy: 2N - 1
• Trisomy: 2N + 1
 Turner Syndrome
• 2N - 1 or 45 chromosomes
Genotype: X_ or X0.
• Phenotype: female, but very poor secondary
sexual development.
 Characteristics
• Short stature.
• Extra skin on neck.
• Broad chest.
• Usually sterile
• Normal mental development except for
some spatial problems.
 Question
• Why are Turner Individuals usually sterile?
• Odd chromosome number.
• Two X chromosomes need for ovary
development.
 Other Sex Chromosome changes
• Kleinfelter Syndrome
• Meta female
• Supermale
 Kleinfelter Syndrome
• 2N + 1
• Genotype: XXY
• Phenotype: male, but sexual development
may be poor. Often taller than average,
mental development fine, usually sterile.
 Meta female
• 2N + 1 or 2N + 2
• Genotype: XXX or XXXX
• Phenotype: female, but sexual development
poor. Mental impairment common.
 Super male
• 2N + 1 or 2N + 2
• Genotype: XYY or XYYY
• Phenotype: male, usually normal, fertile.
 Trisomy events

• Trisomy 21: Down's Syndrome

• Trisomy 13: Patau Syndrome
• Both have various physical and mental
changes.
 Question?
• Why is trisomy more common than
monosomy?
• Fetus can survive an extra copy of a
chromosome, but being hemizygous is usually
fatal.
 Question?
• Why is trisomy 21 more common in older
mothers?
• Maternal age increases risk of nondisjunction.
 Polyploid
• Triploid= 3N
• Tetraploid= 4N
• Usually fatal in animals.
Chromosome Structure Alterations
• Deletions
• Duplications
• Inversions
• Translocations
Translocations
 Results of Translocation
• Loss of genetic information.
• Position effects: a gene's expression is
influenced by its location to other genes.
 Cri Du Chat Syndrome
• Part of p arm of #5 chromosome missing.
• Good survival, but low birth weight and slow
gain.
• Severe mental impairment.
• Small sized heads common.
Cri Du Chat Syndrome
 Philadelphia Chromosome
• An abnormal chromosome produced by an
exchange of portions of chromosomes 9 and
22.
• Causes chronic myeloid leukemia.
 Parental Imprinting of Genes
• Gene expression and inheritance depends on
which parent passed on the gene.
• Usually caused by different methylations of
the DNA.
 Example:
• Prader-Willi Syndrome and Angelman Syndrome
• Both lack a small gene region from chromosome
15.
– Male imprint: Prader-Willi
– Female imprint: Angelman
 Cause:
• Imprints are "erased" in gamete producing
cells and re-coded by the body according to
its sex.
• Gametes are methylated to code as “male “
or “female”.
 Result
• Phenotypes don't follow Mendelian
Inheritance patterns because the sex of the
parent does matter.
 Extranuclear Inheritance
• Inheritance of genes not located on the
nuclear DNA.
• DNA in organelles.
– Mitochondria
– Chloroplasts
 Result
• Mendelian inheritance patterns fail.
• Maternal Inheritance of traits where the trait
is passed directly through the egg to the
offspring.
 Chloroplasts
• Gives non-green areas in leaves, called
variegation.
• Several different types known.
• Very common in ornamental plants.
Variegation in African Violets
Variegated Examples
 Mitochondria
• Myoclonic Epilepsy
• Ragged Red-fiber Disease
• Leber’s Optic Neuropathy
• All are associated with ATP generation
problems and affect organs with high ATP
demands.
 Comment
• Cells can have a mixture of normal and
abnormal organelles.
• Result - degree of expression of the maternal
inherited trait can vary widely.
 Summary
• Know about linkage and crossing-over.
• Sex chromosomes and their pattern of
inheritance.
• Be able to work genetics problems for this
chapter.