CYTO311
CYTOGENETICS
WEEK 11: MODIFICATION OF MENDELIAN RATIOS (PART 2)
Pleiotropy
• Previous examples focused on the effects of two or more
genes on a single characteristic, the converse situation,
where expression of a single gene has multiple
phenotypic effects, is also quite common.
• This phenomenon is referred to as pleiotropy.
• An example is Marfan syndrome, an autosomal dominant
mutation in the gene encoding the connective tissue
protein fibrillin.
• Fibrillin is important to the structural integrity of the eye
lens, to the lining of the blood vessels, to the bones and
other tissues.
• Phenotypes associated with Marfan syndrome includes
lens dislocation, increased risk of aortic aneurism, and
lengthened long bones in limbs.
X-Linkage
• There are chromosomes that determines the sex of an
individual (designated as X and Y chromosomes).
• In humans, males contain an X and a Y chromosome,
while females contain two X chromosomes.
• The remainder of the Y chromosome in humans are
considered to be relatively inert genetically.
• The Y chromosome lacks most genes that are present on
the X.
• Thus, genes present on the X chromosome exhibit unique
patterns of inheritance as compared with autosomal
genes.
X-Linkage in Drosophila
• An example to illustrate X-linkage is the white mutation in
the eyes of Drosophila.
• It has been established that the inheritance patter of the
white-eye trait is clearly related to the sex of the parent
carrying the mutant allele.
• Reciprocal crosses between white-and red-eyed flies did
not yield identical results.
• The conclusion is that the white locus is present on the X
chromosome rather than on one of the autosomes.
BS MEDICAL LABORATORY SCIENCE | CYTO311 | MIDTERM | LAYAN, JAYVHIE
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• It is hypothesized that the recessive allele is found on the
X chromosome, but its corresponding locus is absent
from the Y chromosome.
• Since Y chromosome lacks homology with most genes on
the X chromosome, whatever alleles are present on the
X chromosome of the males will be expressed directly in
their phenotype.
• Males cannot be homozygous or heterozygous for X
linked genes, and this condition is referred to as being
hemizygous.
• One result of X-linkage is the crisscross pattern of
inheritance, whereby phenotypic traits controlled by
recessive X-linked genes are passed from homozygous
mothers to all sons.
X-Linkage in Humans
• In humans, many genes and their respective traits are X-
linked.
• In the pedigree for one form of human color blindness,
the mother in generation I passes the trait to all her sons
but to none of her daughters.
• If the offspring in generation II marry normal individuals,
the color-blind sons will produce all normal male and
female offspring (III-1,2 and 3).
• The normal-visioned daughters will produce normal-
visioned female offspring (III-4,6, and 7), as well as color-
blond (III-8) and normal-visioned (III-5) male offspring.
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 Sex-Limited and Sex-Influenced
• Gene expression may be affected by the gender of an
individual even when genes are not on the X
chromosome.
• Sex-limited –expression of a specific phenotype is
absolutely limited to one gender.
• Sex-influenced –the gender of an individual influences
the expression of a phenotype but the phenotype is
expressed in both genders.
• In both cases, autosomal genes are responsible for the
existence of contrasting phenotypes, but the expression
of such genes is dependent on the hormone constitution
of the individual.
Sex-Limited Inheritance
• Hen feathering is due to dominant allele, H, but
regardless of the homozygous presence of the recessive
h allele, all females remain hen-feathered. Only in males
does the hh genotype result in cock feathering.
Sex-Influenced Inheritance
• Sex-influenced inheritance include pattern baldness in
humans.
• Autosomal genes are responsible for the phenotypes, but
the expression of the genes is dependent on the
hormonal constitution of the individual.
• The heterozygous genotype exhibits one phenotype in
one sex and the contrasting one in the other.
Genetic Background and Environment Affect Phenotypic
Expression
• Phenotypic expression is much more complex
• Gene expression and the resultant phenotype are often
modified through the interaction between an individual’s
particular genotype and the external environment.
Penetrance and Expressivity
• The degree of expression of a particular trait can
be studied quantitatively by determining penetrance and
expressivity.
• Penetrance –the percentage of individuals who show at
least some degree of expression of a mutant genotype.
• Expressivity –reflects the range of expression of the
mutant genotype.
Phenotypic Variation
• Experiments can be used to determine the causes of
phenotypic variation.
• If a lab environment is held constant and extensive
phenotypic variation is still observed, other
genes may be influencing or modifying the phenotype.
BS MEDICAL LABORATORY SCIENCE | CYTO311 | MIDTERM | LAYAN, JAYVHIE
• If genetic background is not the cause of phenotypic
variation, then environmental factors may be involved.
Genetic Background: Position Effects
• The physical location of a gene in relation to other genetic
material may influence its expression.
• If a region of a chromosome is relocated or rearranged,
normal expression of genes in that region may be
modified.
• This is particularly true if the gene is relocated to or near
certain areas of the chromosome that are prematurely
condensed and genetically inert.
Temperature Effects
• Temperature influences phenotype
• In the evening primrose, red flowers are produced when
grown at 23 degrees celsius while white flowers are
produced when grown at 18 degrees.
• In Siamese cats and Himalayan rabbits, dark fur is
exhibited in regions where their body temperature is
slightly cooler (nose, ear and paws).
• It appears that the enzyme responsible for pigment
production is functional only at the lower temperature
present in the extremities
• Temperature-sensitive mutation - mutations whose
expression is affected by temperature.
• An organism carrying a mutant allele may express a
mutant phenotype when grown at one temperature but
express the wild-type phenotype when reared at another
temperature.
Onset of Genetic Expression
• Not all genetic traits become apparent at the same time
during an organism’s life span.
• In most cases, the age at which a mutant gene exerts a
noticeable phenotype depends on events during the
normal sequence of growth and development.
• In humans, the prenatal, infant, preadult, and adult
phases require different genetic information.
• As a result, many sever inherited disorders are not
manifested after birth.
Genetic Anticipation
• Genetic anticipation –phenomenon in which heritable
disorders exhibit a progressively earlier age of onset and
an increased severity of disorder in each successive
generation.
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 Extranuclear Inheritance Maternal Effect

• Organelle heredity –the phenotype is affected by the
expression of genes contained in the DNA of
mitochondria rather than the nucleus.
• Maternal effect –phenotype is determined by the genetic
information expressed in the gamete of the mother;
following fertilization, the developing zygote’s phenotype
is influenced not by the individual’s genotype, but by gene
products directed by the genotype of the mother.
Organelle Heredity
• Also referred to as maternal influence, an offspring’s
phenotype for a particular trait is under the control of the
mother’s nuclear gene products present in the egg.
• The nuclear genes of the female gamete are transcribed
are transcribed, and the genetic products (either proteins
or yet untranslated mRNAs) accumulate in the egg
ooplasm.
• After fertilization, these products are distributed among
newly formed cells and influence patters or traits
established during early development.

• Before discovery of DNA in the mitochondria and

chloroplast, the mechanism of transmission of the traits
were unclear, except that inheritance appeared to be
linked to something in the cytoplasm rather than to genes
in the nucleus.
• Transmission was most often from the maternal parent
through the ooplasm, causing the results of reciprocal
crosses to vary.

Mitochondrial Mutations: Human Genetic Disorders

• The DNA found in the human mitochondria has been

sequenced and contains 16,569 base pairs.
• Mitochondrial gene products include: 13 proteins (for
aerobic cellular respiration), 22 tRNAs (for translation)
and 2 rRNAs (for translation).
• Disruption of any mitochondrial gene may potentially
have a severe impact on the organism.
• Fortunately, a zygote receives a large number of
organelles though the egg so if only one or few of them
contain a mutation, the impact is greatly diluted by the
many mitochondria that lack mutation and function
normally.

Myoclonic Epilepsy and Ragged-Red Fiber Disease

(MERRF)

• Demonstrates inheritance consistent with maternal

transmission.
• Only offspring of affected mothers inherit the disorder,
while offspring of affected fathers are normal.
• Characterized by ataxia, deafness, dementia and
epileptic seizures.
• There is the presence of “ragged-red” skeletal-muscle
fibers that exhibit blotchy red patches due to proliferation
of aberrant mitochondria.

BS MEDICAL LABORATORY SCIENCE | CYTO311 | MIDTERM | LAYAN, JAYVHIE 3