1. The parents are AAbbCcdd and AaBBccDD
Predict the outcome (probability) that:
Offspring will have at least 2 heterozygous traits
Offspring will have at least one recessive trait
Offspring will have all heterozygous traits
Offspring will have at least one homozygous dominant trait

2. The Chromosomal Basis of Inheritance
Chapter 15
The Chromosomal Basis of Inheritance

3. Chromosome Theory of Inheritance
The chromosome theory of inheritance states that
Mendelian genes have specific loci on chromosomes
Chromosomes undergo segregation and independent assortment

4. Fertilization among the F1 plants
The chromosomal basis of Mendel’s laws
Figure 15.2
Yellow-round
seeds (YYRR)
Green-wrinkled
seeds (yyrr)
Meiosis
Fertilization
Gametes
All F1 plants produce
yellow-round seeds (YyRr)
P Generation
F1 Generation
Two equally
probable
arrangements
of chromosomes
at metaphase I
LAW OF SEGREGATION
LAW OF INDEPENDENT ASSORTMENT
Anaphase I
Metaphase II
Fertilization among the F1 plants 9
: 3
: 1 1 4 YR yr yR Y R y r
F2 Generation
Starting with two true-breeding pea plants,
we follow two genes through the F1 and F2
generations. The two genes specify seed
color (allele Y for yellow and allele y for
green) and seed shape (allele R for round
and allele r for wrinkled). These two genes are
on different chromosomes. (Peas have seven
chromosome pairs, but only two pairs are
illustrated here.)
The R and r alleles segregate
at anaphase I, yielding
two types of daughter
cells for this locus.
Each gamete
gets one long
chromosome
with either the
R or r allele. 2
recombines the
R and r alleles
at random. 3
Alleles at both loci segregate
in anaphase I, yielding four
types of daughter cells
depending on the chromosome
arrangement at metaphase I.
Compare the arrangement of
the R and r alleles in the cells on the left and right
Each gamete gets
a long and a short
chromosome in
one of four allele
combinations.
Fertilization results
in the 9:3:3:1
phenotypic ratio in
the F2 generation.
Two alleles for each gene separate during gamete formation
Alleles of genes on nonhomologous chromosomes assort independently during gamete formation

5. Morgan’s Experimental Evidence: Scientific Inquiry
Thomas Hunt Morgan
Provided convincing evidence that chromosomes are the location of Mendel’s heritable factors
Morgan worked with fruit flies
Wild type, or normal, phenotypes that were common in the fly populations (w+)
Traits alternative to the wild type
Are called mutant phenotypes (w)
Because they breed at a high rate
A new generation can be bred every two weeks
They have only four pairs of chromosomes
Figure 15.3

6. Discovery of sex linkage
true-breeding
red-eye female
true-breeding
white-eye male X P
Huh! Sex matters?!
100%
red eye offspring F1
generation
(hybrids)
100%
red-eye female
50% red-eye male
50% white eye male F2
generation

7. What’s up with Morgan’s flies?x x RR rr Rr Rr  r r R r R Rr Rr R RR Rr
Doesn’t work that way! R Rr Rr r Rr rr
100% red eyes
3 red : 1 white

8. Genetics of Sex X Y X XX XY X XX XY
In humans & other mammals, there are 2 sex chromosomes: X & Y
2 X chromosomes
develop as a female: XX
gene redundancy, like autosomal chromosomes
an X & Y chromosome
develop as a male: XY
no redundancy X Y X XX XY X XX XY
50% female : 50% male

9. Let’s reconsider Morgan’s flies…x x
XRXR
XrY
XRXr
XRY Xr Y XR Y  XR XR
XRXr
XRY
XRXR
XRY
BINGO! XR Xr
XRXr
XRY
XRXr
XrY
100% red females
50% red males; 50% white males
100% red eyes

10. How Linkage Affects Inheritance: Scientific Inquiry
Linked genes tend to be inherited together because they are located near each other on the same chromosome
Morgan did other experiments with fruit flies
To see how linkage affects the inheritance of two different characters
Body color
Wild-type: gray body: b+
Mutant: black body: b
Wing Size
Wild type: normal wing: vg+
Mutant: vestigial wing: vg

11. Recombinant (nonparental-type)
Wild Type Mutant
b+ gray body b black body
vg+ normal wing vg vestigial wing
Double mutant
(black body,
vestigial wings)
Wild type
(gray body,
normal wings)
P Generation
(homozygous)
b+ b+ vg+ vg+ x
b b vg vg
F1 dihybrid
(wild type)
b+ b vg+ vg
TESTCROSS
b+vg+
b vg
b+ vg
b vg+
b+ b vg vg
b b vg+ vg
965
(gray-normal)
944
Black-
vestigial
206
Gray-
185
normal
Sperm
Parental-type
offspring
Recombinant (nonparental-type)
RESULTS
EXPERIMENT
Morgan first mated true-breeding
wild-type flies with black, vestigial-winged flies to produce
heterozygous F1 dihybrids, all of which are wild-type in
appearance. He then mated wild-type F1 dihybrid females with black, vestigial-winged males, producing 2,300 F2 offspring, which he “scored” (classified according to
phenotype).
CONCLUSION
If these two genes were on
different chromosomes, the alleles from the F1 dihybrid
would sort into gametes independently, and we would
expect to see equal numbers of the four types of offspring.
If these two genes were on the same chromosome,
we would expect each allele combination, B+ vg+ and b vg,
to stay together as gametes formed. In this case, only
offspring with parental phenotypes would be produced.
Since most offspring had a parental phenotype, Morgan
concluded that the genes for body color and wing size
are located on the same chromosome. However, the
production of a small number of offspring with
nonparental phenotypes indicated that some mechanism
occasionally breaks the linkage between genes on the
same chromosome.
He crossed fruit flies that varied in two characters – body color and wing type

12. Morgan determined that
Genes that are close together on the same chromosome are linked and do not assort independently
Unlinked genes are either on separate chromosomes or are far apart on the same chromosome and assort independently
Heterozygous gray and normal wings
Homozygous black and vestigial
Parents
in testcross
b+ vg+
b vg
b+ vg+
b vg
b vg
Most
offspring X or
Displays gene linkage
Heterozygous gray and normal wings
Homozygous black and vestigial wings

13. Recombinant offspring
Are those that show new combinations of the parental traits
When 50% of all offspring are recombinants
Geneticists say that there is a 50% frequency of recombination for any two genes located on different chromosomes.
Gametes from green-
wrinkled homozygous
recessive parent (yyrr)
Gametes from yellow-round
heterozygous parent (YyRr)
Parental-
type offspring
Recombinant
offspring
YyRr
yyrr
Yyrr
yyRr YR yr Yr yR
Recombination of unlinked genes by independent assortment of chromosomes at metaphase I of meiosis. A 50% frequency of recombination is observed for any two genes that are located on different chromosomes.

14. Linked genes
Exhibit recombination frequencies less than 50% due to crossing over
Figure 15.6
Testcross
parents
Gray body,
normal wings
(F1 dihybrid) b+
vg+ b vg
Replication of
chromosomes
Meiosis I: Crossing
over between b and vg
loci produces new allele
combinations.
Meiosis II: Segregation
of chromatids produces
recombinant gametes
with the new allele 
Recombinant
chromosome
b+vg+
b   vg
b+ vg
b vg+
b vg
Sperm
Meiosis I and II:
Even if crossing over
occurs, no new allele
combinations are
produced.
Ova
Gametes
offspring
b+  vg+
b   vg
b+   vg
b   vg+
965
Wild type
(gray-normal)
b  vg
b  vg+
944
Black-
vestigial
206
Gray-
185
normal
Recombination
frequency =
391 recombinants
2,300 total offspring
100 = 17%
Parental-type offspring
Recombinant offspring
Black body, vestigial wings (double mutant)
Morgan proposed that
Some process must occasionally break the physical connection between genes on the same chromosome
Crossing over of homologous chromosomes was the mechanism that must occasionally break the physical connection between genes on the same chromosome
Recombination frequencies for linked genes are less than 50%, and are dependent on the distance of the genes on the chromosome.

15. Linkage Mapping: Using Recombination Data: Scientific Inquiry
A genetic map
Is an ordered list of the genetic loci along a particular chromosome
Can be developed using recombination frequencies
The further apart two genes are, the higher the probability that a cross-over will occur between them and therefore the higher the recombination frequency

16. A linkage map
Is the actual map of a chromosome based on recombination frequencies
Recombination
frequencies 9%
9.5%
17% b cn vg
Chromosome
The b–vg recombination frequency is slightly less than the sum of the b–cn and cn–vg frequencies because double
crossovers are fairly likely to occur between b and vg in matings tracking these two genes. A second crossover
would “cancel out” the first and thus reduce the observed b–vg recombination frequency.
In this example, the observed recombination frequencies between three Drosophila gene pairs
(b–cn 9%, cn–vg 9.5%, and b–vg 17%) best fit a linear order in which cn is positioned about halfway between
the other two genes:
RESULTS
A linkage map shows the relative locations of genes along a chromosome.
APPLICATION
TECHNIQUE
A linkage map is based on the assumption that the probability of a crossover between two genetic loci is proportional to the distance separating the loci. The recombination frequencies used to construct a linkage map for a particular chromosome are obtained from experimental crosses, such as the cross depicted
in Figure The distances between genes are expressed as map units (centimorgans), with one map unit
equivalent to a 1% recombination frequency. Genes are arranged on the chromosome in the order that best fits the data.
Figure 15.7
The farther apart genes are on a chromosome
The more likely they are to be separated during crossing over
As distance between genes increases, the number of recombinant offspring increases

17. Some genes are so far from each other on a chromosome that crossing over between them is inevitable, driving recombination up to 50%
Same odds as genes on different chromosomes
Genetically unlinked alleles assort independently as if on different chromosomes
Ex: seed color and flower color in pea plants are on the same chromosome, but so far apart they appear to assort independently

18. Many fruit fly genes
Were mapped initially using recombination frequencies
Figure 15.8
Mutant phenotypes
Short
aristae
Black
body
Cinnabar
eyes
Vestigial
wings
Brown
Long aristae
(appendages
on head)
Gray
Red
Normal
Wild-type phenotypes II Y I X IV
III
48.5
57.5
67.0
104.5

19. Recombination/Mapping Problem
Use the following recombination frequencies/percentages to determine the order of these genes on the chromosome. Draw out your final map. Genes a, b, c, d
a,d = 8% a,b = 10% b,d= 18% b,c= 16% a,c= 6%

20. Concept Check 15.2
Genes A, B, and C are located on the same chromosome. Testcrosses show that the recombination frequency between A and B is 28% and between A and C is 12%. Can you determine the linear order of these genes?

21. Human X chromosome Sex-linked usually means “X-linked”
Duchenne muscular dystrophy
Becker muscular dystrophy
Ichthyosis, X-linked
Placental steroid sulfatase deficiency
Kallmann syndrome
Chondrodysplasia punctata,
X-linked recessive
Hypophosphatemia
Aicardi syndrome
Hypomagnesemia, X-linked
Ocular albinism
Retinoschisis
Adrenal hypoplasia
Glycerol kinase deficiency
Incontinentia pigmenti
Wiskott-Aldrich syndrome
Menkes 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
Androgen insensitivity
Chronic granulomatous disease
Retinitis pigmentosa-3
Norrie disease
Retinitis pigmentosa-2
Sideroblastic anemia
Aarskog-Scott syndrome
PGK deficiency hemolytic anemia
Anhidrotic ectodermal dysplasia
Agammaglobulinemia
Kennedy disease
Pelizaeus-Merzbacher disease
Alport syndrome
Fabry disease
Albinism-deafness syndrome
Fragile-X syndrome
Immunodeficiency, X-linked,
with hyper IgM
Lymphoproliferative syndrome
Ornithine transcarbamylase
deficiency
Sex-linked
usually means “X-linked”
more than 60 diseases traced to genes on X chromosome

22. 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
Duchenne muscular dystrophy affects one in 3,500 males born in the United States.
Affected individuals rarely live past their early 20s.
This disorder is due to the absence of an X-linked gene for a key muscle protein, called dystrophin.
The disease is characterized by a progressive weakening of the muscles and loss of coordination.

23. Map of Human Y chromosome?
< 30 genes on Y chromosome
Sex-determining Region Y (SRY)
linked
Channel Flipping (FLP)
Catching & Throwing (BLZ-1)
Self confidence (BLZ-2)
Devotion to sports (BUD-E)
Addiction to death & destruction movies (SAW-2)
Scratching (ITCH-E)
Spitting (P2E)
Inability to express affection over phone (ME-2)
Selective hearing loss (HUH)
Total lack of recall for dates (OOPS)
Air guitar (RIF)

24. Sex-linked genes Follow specific patterns of inheritance
XAXA
XaY Xa Y
XAXa
XAY
XAYa XA
Ova
Sperm
XaYA 
XaYa
A father with the disorder will transmit the mutant allele to all daughters but to no sons. When the mother is a dominant homozygote, the daughters will have the normal phenotype but will be carriers of the mutation.
If a carrier mates with a male of normal phenotype, there is a 50% chance that each daughter will be a carrier like her mother, and a 50% chance that each son will have the disorder.
If a carrier mates with a male who has the disorder, there is a 50% chance that each child born to them will have the disorder, regardless of sex. Daughters who do not have the disorder will be carriers, where as males without the disorder will be completely free of the recessive allele.
(a)
(b)
(c)
Homozygous dominant females appear normal
Heterozygous females are carriers
Homozygous recessive females are diseased
Males are hemizygous
One allele controls gene expression
Heterozygous males are diseased

25. XH Y XHXH XHY XH Xh XHXh XHY XHXh XhY carrier disease
Some recessive alleles found on the X chromosome in humans cause certain types of disorders
Color blindness
Duchenne muscular dystrophy
Hemophilia XH Y
male / sperm
sex-linked recessive
XHXH
XHY XH Xh
female / eggs
XHXh
XHY
XHXh
XhY
carrier
disease

26. X-inactivation XH XHXh Xh 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 and is not expressed
patchwork trait = “mosaic”
patches of black
XH
XHXh
Xh
patches of orange

27. Chromosomal Abnormalities
Errors of Meiosis
Chromosomal Abnormalities

28. Chromosomal abnormalities
Incorrect number of chromosomes
nondisjunction
Homologous chromosomes don’t separate properly during meiosis
breakage of chromosomes
deletion
duplication
inversion
translocation

29. Nondisjunction
Problems with meiotic spindle cause errors in daughter cells
homologous chromosomes do not separate properly during Meiosis 1
sister chromatids fail to separate during Meiosis 2
too many or too few chromosomes 2n
n-1 n
n+1

30. Alteration of chromosome number
error in Meiosis 1
error in Meiosis 2
all with incorrect number
1/2 with incorrect number

31. Nondisjunction 2n+1 2n-1 Aneuploidy Baby has wrong chromosome number
trisomy
cells have 3 copies of a chromosome
monosomy
cells have only 1 copy of a chromosome
n+1 n
n-1 n
trisomy
2n+1
monosomy
2n-1

32. Down syndrome
Trisomy 21
3 copies of chromosome 21
1 in 700 children born in U.S.
Chromosome 21 is the smallest human chromosome
but still severe effects
Frequency of Down syndrome correlates with the age of the mother
Trisomy 13 occurs in about 1 out of every 5,000 live births. It is a syndrome with multiple abnormalities, many of which are not compatible with life. More than 80% of children with trisomy 13 die in the first month. Trisomy 13 is associated with multiple abnormalities, including defects of the brain that lead to seizures, apnea, deafness, and eye abnormalities. The eyes are small with defects in the iris (coloboma ). Most infants have a cleft lip and cleft palate, and low-set ears. Congenital heart disease is present in approximately 80% of affected infants. Hernias and genital abnormalities are common.
Trisomy 18 is a relatively common syndrome affecting approximately 1 out of 3,000 live births, and affecting girls more than three times as often as boys. The presence of an extra number 18 chromosome leads to multiple abnormalities. Many of these abnormalities make it hard for infants to live longer than a few months.
The cri du chat syndrome is caused by the deletion of information on chromosome 5. It is likely that multiple genes on chromosome 5 are deleted. One deleted gene, called TERT (telomerase reverse transcriptase) is involved in control of cell growth, and may play a role in how some of the features of cri cu chat develop. The cause of this rare chromosomal deletion is not known, but it is expected that the majority of cases are due to spontaneous loss of a piece of chromosome 5 during development of an egg or sperm. A minority of cases result from one parent carrying a rearrangement of chromosome 5 called a translocation. Between 1 in 20,000 and 1 in 50,000 babies are affected. This disease may account for up to 1% of individuals with severe mental retardation. Infants with cri du chat syndrome commonly have a distinctive cat-like cry. They also have an extensive grouping of abnormalities, with severe mental retardation being the most important.

33. Down syndrome & age of mother
Mother’s age
Incidence of Down Syndrome
Under 30
<1 in 1000 30
1 in 900 35
1 in 400 36
1 in 300 37
1 in 230 38
1 in 180 39
1 in 135 40
1 in 105 42
1 in 60 44
1 in 35 46
1 in 20 48
1 in 16 49
1 in 12
Rate of miscarriage due to amniocentesis:
1970s data 0.5%, or 1 in 200 pregnancies
2006 data <0.1%, or 1 in 1600 pregnancies

34. Genetic testing Amniocentesis in 2nd trimester Analysis of karyotype
sample of embryo cells
stain & photograph chromosomes
Analysis of karyotype

35. Polyploidy
Is a condition in which there are more than two complete sets of chromosomes in an organism
Figure A tetraploid mammal. The somatic cells of this burrowing rodent has twice as many chromosomes as those of closely related species.
Tetraploidy – 4n – a diploid zygote doesn’t divide after replicating its chromosomes and produces a 4n embryo. Polyploidy seems to have less of an effect on organisms than aneuploidy.

36. Sex chromosomes abnormalities
Human development more tolerant of wrong numbers in sex chromosome
But produces a variety of distinct syndromes in humans
XXY = Klinefelter’s syndrome male
XXX = Trisomy X female
XYY = Jacob’s syndrome male
XO = Turner syndrome female

37. Klinefelter’s syndrome
XXY male
one in every 2000 live births
have male sex organs, but are sterile
feminine characteristics
some breast development
lack of facial hair
tall
normal intelligence

38. Jacob’s syndrome male XYY Males 1 in 1000 live male births
extra Y chromosome
slightly taller than average
more active
normal intelligence, slight learning disabilities
delayed emotional maturity
normal sexual development

39. Trisomy X XXX 1 in every 2000 live births produces healthy females
Why?
Barr bodies
all but one X chromosome is inactivated
How many Barr bodies would you expect?

40. Turner syndrome Monosomy X or X0 1 in every 5000 births
varied degree of effects
webbed neck
short stature
sterile
How many Barr bodies would you expect?

41. Alterations of Chromosome Structure
Breakage of a chromosome can lead to four types of changes in chromosome structure
Deletion
Duplication
Inversion
Translocation
Occurs during meiosis – generally during crossing over
An embryo that is homozygous for a large deletion is missing a number of essential genes – such a deletion is generally lethal

42. Alterations of chromosome structure
Figure 15.14a–d A B C D E F G H
Deletion
Duplication M N O P Q R
Inversion
Reciprocal
translocation
(a) A deletion removes a chromosomal
segment.
(b) A duplication repeats a segment.
- Repeated segment may have been lost in a nearby deletion
(c) An inversion reverses a segment within
a chromosome.
(d) A translocation moves a segment from one chromosome to another,
nonhomologous one. In a reciprocal
  translocation, the most common type,
nonhomologous chromosomes exchange
fragments. Nonreciprocal translocations
also occur, in which a chromosome
transfers a fragment without receiving a
fragment in return.

43. Disorders Caused by Structurally Altered Chromosomes
Cri du chat
Is a disorder caused by a deletion in a chromosome 5
Very severe; infant/childhood death
Certain cancers
Are caused by translocations of chromosomes
Ex: reciprocal translocation of Chromosome 9 and 22 which is associated with Chronic Myelogenous Leukemia
Normal chromosome 9
Reciprocal
translocation
Translocated chromosome 9
Philadelphia
chromosome
Normal chromosome 22
Translocated chromosome 22

44. (a) A wild-type mouse is homozygous for the normal igf2 allele.
Genomic imprinting
Important for embryonic development
Phenotype depends on whether an allele is supplied by the mother or father
Involves the silencing of certain genes that are “stamped” with an imprint during gamete production
(a) A wild-type mouse is homozygous for the normal igf2 allele.
Normal Igf2 allele
(expressed)
with imprint
(not expressed)
Paternal
chromosome
Maternal
Wild-type mouse
(normal size)
Mutant lgf2 allele
Dwarf mouse
Normal size mouse
(b) When a normal Igf2 allele is inherited from the father, heterozygous mice grow to normal size But when a mutant allele is inherited from the father, heterozygous mice have the dwarf phenotype.

45. Inheritance of Organelle Genes
Extranuclear genes
Are genes found in organelles in the cytoplasm
The inheritance of traits controlled by genes present in the chloroplasts or mitochondria
Depends solely on the maternal parent because the zygote’s cytoplasm comes from the egg which contains extranuclear DNA prior to fertilization
Almost all the zygote’s mitochondria are in the cytoplasm of the egg
Mitochondrial genes help make up the protein complexes of the electron transport chain and ATP synthase

46. Some diseases affecting the muscular and nervous systems
Are caused by defects in mitochondrial genes that prevent cells from making enough ATP