Chromosomes and Human Genetics Chapter 12 Chromosomes

1
Chromosomes andHuman Genetics

• Chapter 12

2
Chromosomes Cancer

• Some genes on chromosomes control cell growth and
  division
• If something affects chromosome structure at or
  near these loci, cell division may spiral out of
  control (no brakes at G1)
• This can lead to cancer

3
Philadelphia Chromosome

• First abnormal chromosome to be associated with a
  cancer
• Reciprocal translocation (more on this later)
• Causes chronic myelogenous leukemia (CML)
• Video Gene Therapy to treat Cancer

4
Genes

• Units of information about heritable traits
• In eukaryotes, distributed among chromosomes
• Each has a particular locus
• Location on a chromosome

5
Homologous Chromosomes

• Homologous autosomes (all chromosomes other than
  those that determine sex (X, Y) are identical in
  length, size, shape, and gene sequence
• Sex chromosomes are nonidentical but still
  homologous
• Homologous chromosomes interact, then segregate
  from one another during meiosis

6
Alleles

• Different molecular forms of a gene
• Arise through mutation
• Diploid cell has a pair of alleles at each locus
• Alleles on homologous chromosomes may be same or
  different

7
Sex Chromosomes

• Discovered in late 1800s
• Mammals, fruit flies
• XX is female, XY is male
• Human X and Y chromosomes function as homologues
  during meiosis

8
Karyotype Preparation - Stopping the Cycle

• Cultured cells are arrested at metaphase by
  adding colchicine
• This is when cells are most condensed and easiest
  to identify

9
Karyotype Preparation

• Arrested cells are broken open
• Metaphase chromosomes are fixed and stained
• Chromosomes are photographed through microscope
• Photograph of chromosomes is cut up and arranged
  to form karyotype diagram

10
Figure 12.4Page 197
centrifugation
Obtain cells and arrest them in metaphase with
colchicine
1 2 3 4 5
6 7 8 9 10
11 12
13 14 15 16 17 18
19 20 21 22 XX (or
XY)
11
Animation
Preparation of a karyotype animation.
Click to view animation.
12
Sex Determination
female (XX)
male (XY)
eggs
sperm
Figure 12.5Page 198
13
The Y Chromosome

• Fewer than two dozen genes identified
• One is the master gene for male sex determination
  
• SRY gene (sex-determining region of Y)
• SRY present, testes form testosterone
• SRY absent, ovaries form estrogen, progesterone

14
Effect of YChromosome sex-determining region of
Y (SRY)
appearance of structures that will give rise
to external genitalia
appearance of uncommitted duct system of
embryo at 7 weeks
7 weeks
Y present
Y absent
Y present
Y absent
testes
ovaries
10 weeks
ovary
testis
birth approaching
Figure 12.6Page 199
15
The X Chromosome

• Carries more than 2,300 genes
• Most genes deal with nonsexual traits (ex blood
  clotting)
• Genes on X chromosome can be expressed in both
  males and females

16
Discovering Linkage
homozygous dominant female
recessive male
x
Gametes
X
X
X
Y
All F1 have red eyes
x
Gametes
X
X
X
Y
1/4
1/4
1/4
F2 generation
1/4
Figure 12.7Page 200
17
Discovering Linkage
homozygous dominant female
recessive male
x
Gametes
X
X
X
Y
All F1 have red eyes
Morgan looked at Drosophila melanogaster Reciproc
al crosses
x
Gametes
X
X
X
Y
1/4
1/4
1/4
F2 generation
1/4
Figure 12.7Page 200
18
Linkage Groups

• Genes linked on one type of chromosome (will all
  go to the same gamete, no crossing over in
  Prophase I)
• Fruit flies
• 4 homologous chromosomes
• 4 linkage groups
• Not all genes on chromosome are tightly linked

19
Full Linkage
x
Parents
AB
ab
All AaBb
F1 offspring
meiosis, gamete formation
Genes all go to the same gamete, no crossing over
in Prophase I
Equal ratios of two types of gametes
Figure 12.8aPage 201
50 AB
50 ab
20
Incomplete Linkage
AC
ac
x
Parents
F1 offspring
All AaCc
Some genes crossing over in Prophase I
meiosis, gamete formation
a
a
A
A
Unequal ratios of four types of gametes
C
c
C
c
parental genotypes
recombinant genotypes
Figure 12.8bPage 201
21
Crossover Frequency
Proportional to the distance that separates genes
A
B
C
D
Crossing over will disrupt linkage between A and
B (bigger distance between) more often than C and
D (shorter distance between)
In-text figurePage 201
22
Linkage Mapping in Humans

• Linkage maps based on pedigree analysis through
  generations
• Color blindness and hemophilia are very closely
  linked on X chromosome
• Can be transmitted from mother who is the carrier
• Incomplete linkage may show only color blindness
  or hemophilia, not both, due to crossing over
  (genetic recombination)

23
Genetic Abnormality

• A rare, uncommon version of a trait
• Polydactyly
• Unusual number of toes or fingers (6)
• Does not cause any health problems
• View of trait as disfiguring is subjective

24
Pedigree (chart of genetic connections) Symbols
male
female
marriage/mating
offspring in order of birth, from left to right
Individual showing trait being studied
sex not specified
generation
I, II, III, IV...
Figure 12.9aPage 202
25
Pedigree for Polydactyly
Black s fingers Blue s toes
male
female
5,5 6,6

5,5 6,6
6,6 5,5
6,6 5,5
6
7
5,5 6,6
5,5 6,6
5,5 6,6
5,5 6,6
5,6 6,7
12
6,6 6,6
Figure 12.9bPage 202
26
Animation
Human pedigree diagram animation.
Click to view animation.
27
Genetic Disorders (p. 203)

• Inherited conditions that cause mild to severe
  medical problems (syndrome has a set of symptoms
  that characterize the disorder diseases have
  symptoms too, but are illness caused by
  infectious, dietary, or environmental factors,
  NOT by inheritance)
• Why dont genetic disorders disappear?
• Mutation introduces new rare alleles
• In heterozygotes, harmful allele is masked, so it
  can still be passed on to offspring

28
Autosomal Recessive Inheritance Patterns

• If parents are both heterozygous, child will have
  a 25 chance of being affected

Figure 12.10aPage 204
29
Galactosemia

• Caused by autosomal recessive allele
• Gene specifies a mutant enzyme in the pathway
  that breaks down lactose
• Galactose accumulates to toxic levels damage to
  eyes, liver, brain, and causes malnutrition,
  diarrhea, and vomiting

Remedy eliminate all dairy products in diet
In-text figurePage 204
30
Autosomal Dominant Inheritance

• Trait typically appears in every generation

Figure 12.10bPage 204
31
Animation
Autosomal-recessive inheritance interaction.
Click to view animation.
32
Huntington Disorder

• Autosomal dominant allele
• Expressed even in heterozygotes
• Causes involuntary movements, nervous system
  deterioration, death
• Symptoms dont usually show up until person is
  past age 30
• People often pass allele on before they know they
  have it
• Video Huntington Disorder

33
Achondroplasia

• Autosomal dominant allele
• In homozygous form usually leads to stillbirth
• Heterozygotes display a type of dwarfism
• Have short arms and legs relative to other body
  parts

34
X-Linked Recessive Inheritance (color blindness,
hemophilia, fragile X syndrome)

• Males show disorder more than females
• Son cannot inherit disorder from his father (he
  gets his maleness Y from dad)

Figure 12.12aPage 205
35
Examples of X-Linked Traits

• Color blindness
• Inability to distinguish among some colors
• Hemophilia
• Blood-clotting disorder
• 1/7,000 males has allele for hemophilia A
• Was common in European royal families

36
Fragile X Syndrome

• An X-linked recessive disorder
• Causes mental retardation
• Mutant allele for a gene that normally would
  specify a protein required for brain development
• Allele has repeated segments of DNA (duplications)

37
Hutchinson-Gilford Progeria

• Mutation causes accelerated aging
• No evidence of it running in families
• Appears to be dominant
• Seems to arise as spontaneous mutation
• Usually causes death (heart attack, stoke) in
  early teens

38
Duplication

• Gene sequence that is repeated several to
  hundreds of times
• Duplications occur in normal chromosomes
• May have adaptive advantage
• Useful mutations may occur in copy

39
Duplication
normal chromosome
one segment repeated
three repeats
40
Inversion

• A linear stretch of DNA is reversed
• within the chromosome

segments G, H, I become inverted
In-text figurePage 206
41
Translocation

• A piece of one chromosome becomes attached to
  another nonhomologous chromosome
• Most are reciprocal
• Philadelphia chromosome (1st cancer chromosome)
  arose from a reciprocal translocation between
  chromosomes 9 and 22

42
Translocation
In-text figurePage 206
one chromosome
a nonhomologous chromosome
nonreciprocal translocation
In-text figurePage 206
43
Deletion

• Loss of some segment of a chromosome
• Most are lethal or cause serious disorder
• Cri-du-chat mental impairment and abnormal
  larynx (cats meow)

44
Aneuploidy

• Individuals have one extra or less chromosome
• (2n 1 or 2n - 1)
• Major cause of human reproductive failure
• Most human miscarriages are aneuploids

45
Polyploidy

• Individuals have three or more of each type of
  chromosome (3n, 4n)
• Common in flowering plants
• Lethal for humans
• 99 die before birth
• Newborns die soon after birth

46
Nondisjunction (Down-XXX, Turner-X, and
Klinefelter-XXY Syndromes)
n 1
n 1
n - 1
chromosome alignments at metaphase I
n - 1
nondisjunction at anaphase I
alignments at metaphase II
anaphase II
Figure 12.17Page 208
47
Down Syndrome (nondisjunction)

• Trisomy of chromosome 21 (XXX)
• Mental impairment and a variety of additional
  defects (heart defects, respiratory and digestive
  problems)
• With good medical care, can live to age 55
• Can be detected before birth
• Risk of Down syndrome increases dramatically in
  mothers over age 35

48
Turner Syndrome (nondisjunction)

• Inheritance of only one X (XO)
• 98 spontaneously aborted
• Survivors are short, infertile females
• No functional ovaries
• Secondary sexual traits reduced
• May be treated with hormones, surgery

49
Klinefelter Syndrome

• XXY or XXXY condition
• Results mainly from nondisjunction in mother
  (67)
• Phenotype is tall, overweight males
• Sterile or nearly so
• Feminized traits (sparse facial hair, somewhat
  enlarged breasts)
• Treated with testosterone injections

50
XYY Condition (nondisjunction)

• Taller than average males
• Most otherwise phenotypically normal
• Some mentally impaired
• Once thought to be predisposed to criminal
  behavior, but studies now discredit (no double
  blind studies same investigator for processing
  karyotypes and personal histories)

51
Nondisjunction Disorder Summary
XXY
XX
x
Y
(Klinefelter syndrome)
gamete
XX
or
XXX
XX
X
x
(metafemale)
nondisjunction
XX
YO
O
x
Y
(not viable)
or
O
gamete
XO
O
X
x
(Turner syndrome)
meiosis and gamete formation
possibilities at fertilization
genotype (phenotype)
52
Phenotypic Treatments

• Symptoms of many genetic disorders can be
  minimized or suppressed by
• Dietary controls (phenylketonuria (PKU avoid
  products with aspartame reduce intake of
  phenylalanine), diabetes, and galactosemia)
• Adjustments to environmental conditions
  (albinism, sickle-cell anemia)
• Surgical treatments (cleft lip or palate)
• Hormonal treatments (Turner and Klinefelter
  Syndromes)

53
Genetic Screening

• Large-scale screening programs detect affected
  persons
• Newborns in United States routinely tested for
  PKU
• Early detection allows dietary intervention and
  prevents brain impairment

54
Prenatal Diagnosis

• Amniocentesis fluid sampled from amnion
  sloughed fetal cells
• Chorionic villus sampling chorion (sac
  surrounding the amnion) cells sampled
• Fetoscopy fiberoptic device can diagnose
  sickle-cell anemia and hemophilia
• All methods have some miscarriage risks

55
Animation
Amniocentesis animation.
Click to view animation.
56
Preimplantation Diagnosis

• Used with in-vitro fertilization
• Mitotic divisions produce ball of 8 cells
  (embryo)
• All cells have same genes
• One of the cells is removed and its genes
  analyzed
• If cell has no defects, the embryo is implanted
  in uterus