Chapter 15: The Chromosomal Basis of
Inheritance
Overview: Locating Genes Along Chromosomes
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Today we can see the location of a particular gene by tagging chromosomes with a fluorescent
dye that highlights that gene
15.1 Mendelian inheritance has its physical basis in the behavior of
chromosomes
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People started noticing the parallels between chromosomes and genes, and the chromosome
theory of inheritance began to form
o Chromosome theory of inheritance—Mendelian genes have specific loci (positions)
along chromosomes, and it is the chromosomes that undergo segregation and
independent assortment
The behavior of homologous chromosomes during meiosis accounts for the segregation of
alleles at each genetic locus to different gametes
o The behavior of chromosomes during meiosis in the F₁ generation and subsequent
random fertilization give rise to the F₂ phenotypic ratio observed by Mendel
Morgan’s Experimental Evidence: Scientific Inquiry
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First solid evidence associating a specific gene with a specific chromosome came from Thomas
Hunt Morgan
Morgan’s Choice of Experimental Organism
 Morgan used the Drosophila melanogaster (fruit fly) to do his experiments because a single
mating produces hundreds of offspring and a new generation can be bred every two weeks
o Also the fruit fly only has four pairs of chromosomes that are easily distinguishable with
a light microscope
 Wild type—the phenotype for a character most commonly observed in natural populations
o Ex: red eyes in Drosophila
o Mutant phenotypes—traits that are alternatives to the wild type
Correlating Behavior of a Gene’s Alleles with Behavior of a Chromosome Pair
 When Morgan bred the F1 flies there was the typical F2 offspring, but the white eye trait
showed up only in males
o All F2 females had red eyes, while half the males had red eyes and half had white eyes
 Therefore, Morgan concluded that somehow a fly’s eye color was linked to its
sex
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It appears only in males because they only have one X chromosome and
no corresponding allele on the Y chromosome, so if they get the
recessive allele, they have white eyes cause there’s no other one to
offset it, whereas a female would have two
15.2 Sex-linked genes exhibit unique patterns of inheritance
The Chromosomal Basis of Sex
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Females have XX chromosomes, males have XY
Short segments at either end of the Y chromosomes are the only regions that are homologous
with corresponding regions of the X—this allow the X and Y chromosomes to pair during meiosis
In testes and ovaries the two sex chromosomes separate during meisois and each gamete
receives one
o The egg will always have X, but half sperm cells will have X and half will have Y—if the
egg meets with an X, they have a girl; if it meets with the Y, they have a boy
Before 2 months, the embryo’s gonads are generic—if they have a Y chromosome it has the SRY
(sex determining region of Y) gene that is required for the development of testes—if it’s not
there (because there’s no Y chromosome) the gonads will go ahead and develop into ovaries
There are 78 genes on the human Y chromosome that code for about 25 proteins—half of these
genes are expressed only in the testis and some are needed for normal testicular functioning
o In their absence the person is male but doesn’t produce normal sperm
Inheritance of Sex-Linked Genes
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Sex-linked gene—a gene located on either sex chromosome—in humans though the term refers
specifically to a gene on the X chromosome
o Father pass sex-linked alleles to all of their daughters but none of their sons, moms can
pass sex linked to both sons and daughters
If sex-linked trait is due to recessive allele, females only show the phenotype if she’s
homozygous recessive, but since guys only have one locus for the gene because they only have
one X chromosome, they’ll show it if their ex chromosome has it—called hemizygous
o Because of this more males than females have sex-linked recessive disorders
Some sex-linked recessive disorders:
o Color blindness
o Duchenne muscular dystrophy—characterized by a progressive weakening of the
muscles and loss of coordination
 affects about one out of every 3,500 males born in the US
 affected people rarely live past 20s
 caused by lack of key muscle protein called dystophin
o hemophilia—defined by the absence of one or more of the proteins required for blood
clotting
 when an affected person is injured bleeding is prolonged
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treated today with intravenous interjections of the missing protein
X Inactivation in Female Mammals
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on X chromosome in each cell in females becomes almost totally inactivated during embryonic
development so that cells of females and males have the same EFFECTIVE dose of these genes
o Barr body—lies along the inside of the nuclear envelop—inactive X that compacts into a
small object
 Most genes of the Barr body aren’t expressed but in the ovaries these Barr body
chromosomes are reactivated in the cells that give rise to eggs so when they
split every female gamete has an active X
Selection of which X chromosome will form the Barr body occurs randomly and independently in
each embryonic cell, so females consist of a mosaic of two types of cells:
o The ones with active X from the father and ones with the active X from the mother
 Once X chromosome is inactivated in a particular cell all mitotic descendants of
that cell have the same inactive X
 So, if a female’s heterozygous then about half her cells will express one
allele and the others will express the alternate
o In cats mosaicism results in mottled coloration of tortoiseshell
fur
o In humans it can be seen in a recessive X linked mutation that
prevents development of sweat gland—woman who’s
heterozygous for this has patches of normal skin and patches of
skin lacking sweat glands
Inactivation of X chromosomes involves modification of DNA
o Attachment of methyl groups to one of nitrogenous bases of DNA nucleotides
o X chromosome gene XIST (X inactive specific transcript) that is active only in Barr-body
chromosome
15.3 Linked genes tend to be inherited together because they are located
near each other on the same chromosome
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Each chromosome has hundreds or thousands of genes
Linked genes—genes located on the same chromosome that tend to be inherited together in
genetic crosses
o When geneticists follow linked genes in breeding experiments, results deviate from
expected from Mendel’s law of independent assortment
How Linkage Affects Inheritance
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Mendel did some more experiments and basically concluded that genes are usually inherited
together in specific combos because the genes for these characters are on the same
chromosome BUT they’re only partly linked genetically
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To understand this you have to know genetic recombination—production of offspring with
combinations of traits that differ from those found in either parent
Genetic Recombination and Linkage
Recombination of Unlinked Genes: Independent Assortment of Chromosomes
 Some offspring have traits that do not match those of the parents
o Ex: pea plant with yellow round seeds that’s heterozygous (YyRr) crossed with a plant
with green wrinkled seeds that’s homozygous for both (yyrr) makes yellow round and
green wrinkled, but also green round and yellow wrinkled
 Parental types—offspring who phenotypes match the parental phenotypes
 Recombinant types (recombinants)—the nonparental phenotypes that have different combos
of traits
o 50% frequency of recombination is observed in such testcrosses for any two genes that
are located on different chromosomes and thus unlinked—this recombination occurs
from independent assortment
Recombination of Linked Genes: Crossing Over
 In fruit fly study for body color and wing type, most offspring had parental phenotypes
o This suggested that the two genes were on the same chromosome, since the occurrence
of parental types with a frequency of greater than 50% indicated linked genes
 However, about 17% of offspring were recombinants
o Morgan said this happened because some process must occasionally break the physical
connection between linked genes
 Now we know this as crossing over—accounts for recombination of linked genes
o Crossing over happens while replicated homologous chromosomes are paired during
meiosis I and a set of proteins orchestrates an exchange of corresponding segments of
one maternal and one paternal chromatid—basically end portions of two nonsister
chromatids trade places with each other
 Recombinant chromosomes resulting from crossing over may bring alleles together in new
combinations and then meiosis distributes the recombinant chromosomes to gametes
 Percentage of recombinant offspring (recombination frequency) is related to the distance
between linked genes
Mapping the Distance Between Genes Using Recombination Data: Scientific
Inquiry
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Genetic map—an ordered list of the genetic loci along a particular chromosome
o made by Sturtevant who thought that recombination frequencies depend on the
distance between genes on a chromosome—the assumed that crossing over is random
and the chance of crossing over approximately equal at all points along a chromosome
based on this he predicted that the farther apart two genes are, the higher probability that
crossover will occur between them and therefore the higher the recombination frequency
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linkage map—a genetic map based on recombination frequencies
map units—the distances between genes—one map unit is equivalent to 1% recombination
frequency
o today they’re usually called centimorgans
it’s a little more complicated than all this—some genes that are on the same chromosome act
like they’re not linked
linkage map does portray order of genes along a chromosome, but it does not accurately
portray the precise locations of those genes
cytogenetic maps—locate genes with respect to chromosomal features
15.4 Alterations of chromosome number or structure cause some
genetic disorders
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large scale chromosomal changes can effect organism’s phenotype
Abnormal Chromosome Number
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nondisjunction—the members of a pair of homologous chromosomes don’t move apart
properly during meiosis I or sister chromatids fail to separate during meiosis II
o one gamete receives two of the same type of chromosome and another gamete
receives no copy—other chromosomes are usually distributed normally
aneuploidy—when a zygote has an abnormal number of a chromosome (may involve more than
one chromosome)
o happens if an abnormal gamete unites with a normal one
o if the zygote doesn’t get a copy of the chromosome, the aneuploid zygote is monosomic
for that chromosome
 the cell has 2n -1 chromosomes
o if the zygote has the chromosome present in the triplicate (so the cell has 2n + 1
chromosomes) then the aneuploid cell is trisomic for that chromosome
mitosis makes the anomaly go in to all embryonic cells and if the organism survives it usually has
a set of traits caused by the abnormal dose of the genes associated with the extra or missing
chromosome
some organisms have more than two complete chromosome sets in all somatic cells—
polyploidy
o triploidy (3n)
 can come from the fertilization of an abnormal diploid egg produced by
nondisjuntion of all of its chromosome
o tetraploidy (4n)
 could result from the failure of a 2n zygote to divide after replicating its
chromosomes
o this is farily common in plant kingdom :
 bananas are triploid and wheat is hexaploid
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o in animal kingdom it’s not so common
on extra chromosome disrupts genetic balance more than does an entire extra set of
chromosomes
Alterations of Chromosome Structure
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errors in meiosis or damaging agents like radiation can cause breakage of a chromosome which
can lead to four types of changes in chromosome structures:
o deletion—occurs when chromosomal fragment is lost and the affected chromosome is
then missing certain genes
o duplication—when the “deleted” fragment from a deletion is attached as an extra
segment to a sister chromatid
 detached fragment can also attach to a nonsister chromatid of a homologous
chromosome but in that case the duplicated segments might not be identical
because the homologs could carry different alleles of certain genes
o inversion—when a chromosomal fragment may also reattach to the original
chromosome but in reverse orientation
o translocation—when the fragment joins a nonhomologous chromosome
deletions and duplications are likely to happen during meiosis because during crossing over
nonsister chromatids sometimes exchange unequal sized segments of DNA which means one
chromosome has a deletion and one has a duplication
o if a diploid embryo that is homozygous for a large deletion (or has a single X
chromosome with a large deletion in a male) is usually missing a number of essential
genes and this is lethal
o duplications and translocations are harmful too
 alter phenotype because a gene’s expression can be influenced by its location
among neighboring genes
Human Disorders Due to Chromosomal Alterations
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most times aneuploidy makes embryos spontaneously abort long before birth, but sometimes
they result in individuals with certain aneuploid conditions who can survive to birth and beyond
o these people have a set of traits—syndrome—that’s characteristic of the type of
aneuploidy
Down Syndrome (Trisomy 21)
 Down syndrome—the result of an extra chromosome 21 so that each body cell has a total of 47
chromosomes
o Affects on out of every 700 children born in the US
o Includes characteristic facial features, short stature, heart defects, susceptibility to
respiratory infection, and mental retardation
o People with Down syndrome are prone to developing leukemia and Alzheimer’s
o On average have a shorter life span than normal
o Most are sexually underdeveloped and sterile
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Frequency increases with age of mother:
o Occurs in .04% of children born to women under 30
o .92% for mothers at age 40 and keeps going up
Most cases result from nondisjunction during meiosis I
Aneuploidy of Sex Chromosomes
 Most conditions from nondisjunction of sex chromosomes appear to upset genetic balance less
than aneuploid conditions involving autosomes
 Extra X chromosome in a male occurs once in every 2,000 live births
o Called Klinefelter syndrome
o People have male sex organs but the testes are abnormall small and the man is sterile
o The extra x chromosome is inactivated but some breast enlargement and other female
body characterists is common
o Affected may have subnormal intelligence
 Some males have an extra Y chromosome
o Not any well defined syndrome, but they tend to be somewhat taller than average
 Some females have trisomy X (XXX)
o Occurs once in 1,000 births
o Healthy and can’t be distinguished except through karyotype
 Monosomy X—Turner Syndrome
o Occurs once in every 5,000 births
o Only known viable monosomy in humans
o Phenotypically female but are sterile because their sex organs don’t mature
o Most have normal intelligence
Disorders Caused by Structurally Altered Chromosomes
 Many deletions in human chromosomes (even in heterozygous state) cause sever problems
o Ex: cri du chat (cry of the cat) results from a specific deletion in chromosome 5—child is
mentally retarded, has a small head with unusual facial features and has a cry that
sounds like a cat mewing—they usually die in infancy or early childhood
 Chromosomal translocations are implicated in certain cancers
o Ex: chronic myelogneous leukemia (CML)—occurs when a reciprocal translocation
happens during mitosis of cells that become white blood cells
 Exchange of large part of chromosome 22 with small part from tip of
chromosome 9 produces a much shortened 22 called the Philadelphia
chromosome
15.5 Some inheritance patterns are exceptions to the standard
chromosome theory
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Two normally occurring exceptions to Mendelian genetics: one involves genes located in nucleus
and other involves genes located outside the nucleus
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In both the sex of the parent contributing the allele is a factor
Genomic Imprinting
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Two to three dozen traits have been identified in mammals that depend on which parents
passed along the alleles for those traits
o Called genomic imprinting—variation in phenotype depending on whether an allele is
inherited from the male of female parent
Genomic impritng happens during formation of gametes and silences on allele of a certain gene
o Because the genes are imprinted differently in sperm and eggs, zygote expresses only
one allele of imprinted genes—either the one from the male or female and it’s
expressed in every cell
A gene imprinted for maternal allele expression is always imprinted for maternal allele
expression, generation after generation
What is genomic imprint?:
o Methyl groups that are added to cytosine nucleotides—this may silence the allele or
sometimes activate the expression
Imprinting affects only a small number of genes but they’re very critical for embryonic
development
o Normal development requires that embryonic cells have exactly one active copy of
certain genes
Inheritance of Organelle Genes