The Chromosomal Basis of Inheritance

1
Chapter 15

• The Chromosomal Basis of Inheritance

2
TOPICS FOR TODAYS LECTURE

• Morgan Strutevant
• Sex Chromosomes
• Linked Genes
• Gene Map
• Why you are smarter than Sarah Palin
• Human Genetic Disorders

3
Chromosome theory of inheritance supported
Mendels laws

• (what are mendels laws?)
• 1.
• 2.

4
Chromosome theory of inheritance supported
Mendels laws

• 1. Law of Segregation- pairs of factors
  separate during gamete formation
• 2. Law of Independent Assortment- separated
  pairs of factors sort themselves into gametes
  independently of each other.

5

• THOMAS HUNT MORGAN was the first scientist to
  associate a specific gene with a specific
  chromosome. His experiments provided convincing
  evidence that chromosomes are the location of
  Mendels heritable factors.

Gene stained with fluorescent dye shows the same
locus on homologous chromosomes.
6
Experimental organism
Fruit fly Drosophila melanogaster
7
Discovery of Sex Linkage(sex experiments w/
flies creepy)

• Cross 1
• P generation
• (pure breeding)
• F1 results all had red eyeswild type
• Suggests dominance
• like Mendels experiment

white-eyed (mutant) male
red-eyed (wild-type) female
X
8

• CROSS 2 (bro x sis)
• F1 x F1 F2
• F2 results
• 3 wild type 1 mutant
• Except that
• only males are mutant
• all the females are wild type and
• Males are mutant 1/2 of the time.

9
Figure 15.3 Sex-linked inheritance
Red is wild type White is mutant F1- all are
wild type F2- all of the females are wild type.
1/2 males are wild type Discovered Sex
chromosomes The gene for eye color was Inherited
differently among Male and female flies in the
F2. Difference x y chromosomes Genes located
on a sex chromosome Are called X LINKED. Or Y
LINKED
10
GENE LINKAGE MAPS

• The number of genes in a cell is far greater than
  the number of chromosomes in fact, each
  chromosome has hundreds or thousands of genes.
• Thus, linked genes tend to be inherited together.

11
Gene Linkage and Map Units

• Gene linkage was explained by Thomas Hunt Morgan
  in 1910.
• When he was examining traits of the fruit fly-
• Drosophila melanogaster.
• Why study the fruit fly?
• Great for research because it was benign
  (harmless) unlike MEDFLY
• Reproductive cycle 2 weeks
• Small genome 2n is 8
• -so great for genetic research.

12
Gene Linkage and Map Units

• Genes are said to be LINKED when they
• exist on the same chromosome
• and they are inherited together.

The genes of chromosome 9 are LINKED.
13
Gene Linkage and Map Units

• When genes are linked, the expected phenotype
  ratios during breeding experiments deviate from
  the Mendelian ratios of
• 1) F1 xF1 dihybrid cross
• Ex (AaBb x AaBb)
• F2 9331
• More importantly
• 2) F1 dihybrid test cross
• Ex (AaBb x aabb)
• F2 1111

14
Unnumbered Figure (page 272) Drosophila testcross
15
For Example

• Parents who were pure for two traits (homozygous)
  were crossed (AABB x aabb).
• The F1 generation produced individuals that were
  heterozygous for both traits. (AaBb)
• An F1 individual is test-crossed with a
  homozygous recessive individual. (AaBb x aabb)
• If both genes were located on different
  chromosomes the expected phenotypic ratio should
  be 1111.
• The actual ratios suggested that the genes DID
  NOT assort independently. Most of the phenotypes
  matched the P1 generation parents.

16

• Recombinant phenotypes (those different from
  either P1 gen parents) were the result of
  crossing over instead of independent assortment.

17
The recombination frequency can be calculated by
dividing the total number of recombinants by
the total number of offspring.
18
Figure 15.5b Recombination due to crossing over
19

• One of Morgans students, Alfred Sturtevant came
  up with a method for constructing a genetic map,
  showing the position of genes on a chromosome.
• An important observation the recombination
  frequencies reflect the distances between genes.
• Therefore, genes farther apart have a greater
  chance of being separated by crossing over.
• As the distance between genes increases, so does
  their recombination frequency.
• The distance between genes are expressed in map
  units where one map unit 1 recombination
  frequency.
• Map units are called centimorgans, in honor of
  Morgan.

20
(No Transcript)
21
Morgans work Evidence of linked genes in
drosophila. Evidence of the chromosomal basis
of inheritance.
22
WHY YOU ARE SMARTER THAN SARAH PALIN
Where does a lot of that earmark money end up
anyway? You've heard about some of these pet
Projects they really don't make a whole lot of
sense and sometimes these dollars go to projects
that have little or nothing to do with the
public good. Things like fruit fly research in
Paris, France. I kid you not.
Palin "fruit fly research"
23
(No Transcript)
24
Next- human genetic disorders.

• http//www.youtube.com/watch?vEg1vIeuQT1s

25
Chapters 14 15Genetic Diseases Disorders
26
What is the difference between an infectious
disease and a genetic one???

• Infectious illnesses/ diseases caused by
  microorganisms virus, bacteria, protists, fungi,
  tiny animals (worms) that harm cells.
• They can be transmitted from one host to
  another contagious.
• Genetic is inherited. Defect in the DNA code.

27
GENETIC DISEASES/DISORDERS

• Thousands of genetic disorders are caused by
  recessive genes (mutations in DNA).
• Some are mild and some are deadly.
• Most of these alleles code for a malformed
  protein or for creating no protein at all.
• NOT CONTAGIOUS, but can be transmitted to
  offspring.

28
Inheritance Patterns of Genetic Disorders

1. Autosomal Recessive gg disease
2. Autosomal Dominant Gg disease
3. Autosomal Codominant
4. Sex Linked Recessive XgXg XgY disease
5. Sex Linked Dominant XGXg XGY disease
6. ANEUPLOIDY of autosomes (too many/few) disease
7. ANEUPLOIDY of sex chromosomes
8. CHROMOSOME alteration during crossing over

29
Examples of recessively inherited disorders
(autosomal recessive)

• Cystic fibrosis most lethal disease in the US
• Caused by defective chloride membrane channels.
• Leads to thick mucus building up in the lungs,
  digestive tract low weight, susceptible to
  respiratory infections.
• 2) Tay-Sachs caused by a dysfunctional enzyme
  
• that no longer breaks down fats.
• Leads to fatty build-up in the brain and around
  nerves. Accumulation of the lipids in brain cells
  causes progressive nervous system dysfunction and
  is usually fatal by age four.

30

• 3) Phenylketonuria (PKU) inability to properly
  break down the amino acid phenylalanine.
  Untreated causes mental retardation. Managed with
  restricted diet low in phenylalanine.

31

• Ex. AUTOSOMAL CODOMINANT disorder
• Sickle Cell caused by a single amino acid
  substitution in hemoglobin. Red blood cells of
  individuals with this defect are unable to
  effectively transport oxygen throughout the body.
  
• (Pleiotropic effect on multiple organs)

32

• Ex. AUTOSOMAL DOMINANT disorders
• Huntingtons disease is a degenerative disease
  of the nervous system, the allele expresses
  itself later in life so although it is caused by
  a single allele and is lethal, it may already be
  passed on to the next generation.
• Achondroplasia (dwarfism)
• Characterized by problems with bone growth.
• Also polydactyl

33

• Sex Linked Disorders Patterns of Inheritance
• NO heterozygote among males because the gene is
  on the X chromosome males are XY. Heterozygous
  females are carriers.
• Sex linked recessive Males more susceptible to
  disease.
• 1. ALD (adreno leuko dystrophy)- sex linked
  recessive
• 2. Red-Green Color Deficiency- sex linked
  recessive
• 3. Hemophilia- sex linked recessive
• Sex linked dominant Females more susceptible to
  disease.
• 1.Duchennes Muscular Dystrophy- sex linked
  DOMINANT

34
In humans, such X linked inheritanceIs
designated XCXC XCXc XCXC XcY XCY
Ishihara color blindness test
Red Green Color Blindness is much more
prevalent among males.
35

• Hemophilia- inability to code for all factors
  required to form normal blood clots. Surface
  wounds ok.
• Duchennes Muscular Dystrophy- Absence of an
  essential muscle protein. Results in
  deteriorating muscles and loss of coordination.
• (sex linked dominant- so females are more likely
  to show the disorder than other x-linked ones)

36
HEMOPHELIA
Large hemorrhage surface wounds are slow to heal
but not Fatal- it is the internal bleeding and
tissue wounds that are a problem
37
Hemo (blood) Philia (family)
38

• EUROPEAN ROYALTY AND HEMOPHILIA
• History's most famous carrier of the gene for
  hemophilia was Victoria (1819-1901), Queen of
  England and grandmother to most of the royalty in
  Europe. In 1853, Queen Victoria gave birth to her
  eighth child, Leopold, Duke of Albany, who had
  hemophilia and died at the age of 31 from
  internal bleeding after a fall.
• Two of Queen Victoria's four daughters, Alice (b.
  1843) and Beatrice (b. 1857), also carried the
  gene for hemophilia and subsequently transmitted
  the disease to three of Victoria's grandsons and
  to six of her great-grandsons.
• Alice's daughter Alexandra also was a carrier of
  hemophilia, and she transmitted the disease to
  her son Alexis (b. 1904), whose father was Czar
  Nicholas 11 (18681918) of Russia. Alexis is
  perhaps the most famous of the European royals
  with hemophilia. Alexis was the heir to his
  father's throne and his medical condition caused
  much anxiety in the royal household. Historians
  are still discussing the role Alexis's condition
  played in the Russian revolution of 1918.

39
Autosomal chromosome disorders

• If an organism is born with an abnormal number of
  chromosomes it is called aneuploidy.
• It is caused by nondisjunction of homologous
  chromosomes during meiosis.
• The chromosomes fail to separate and one gamete
  receives both copies and the other gamete
  receives none.

40
Down syndrome or Trisomy 21 is caused by having
three copies of the 21st chromosome.
41
Sex Chromosome disorders

• X inactivation during embryonic development in
  females one X chromosome randomly condenses into
  an inactive mass (called a Barr body) within each
  cell so each cell has only one active X
  chromosome.
• The result most of the alleles on the X
  chromosome are expressed individually.
• X-inactivation, is an epigenetic change that
  results in a different phenotype but is not a
  change at the genotypic level.
• This can give rise to mild symptoms in female
  carriers of X-linked genetic disorders.
• Reversed in the female germline, so that all
  oocytes contain an active x chromosome

42

• In cats this leads to tortoiseshell coloration
  because in
• Some cells one x is inactive and in others, the
  other is.
• In humans females will express recessive disease
  alleles
• more frequently EX faulty sweat glands in some
  areas.

43
Figure 15.10x Calico cat
44

• 2) Nondisjunction of SEX CHROMOSOMES
• a)XXY individuals Klinefelter syndrome
• Male sex organs
• Small, sterile testes
• Female body characteristics, including some
  breast development

45

• 2) Nondisjunction of SEX CHROMOSOMES
• a)XXY individuals Klinefelter syndrome
• Male sex organs
• Small, sterile testes
• Female body characteristics, including some
  breast development
• XYY individuals no associated syndrome
• Taller than average
• c) XXX individuals super females (trisomy x)
  taller than average, slightly lower intelligence
• XO individuals Turner syndrome
• Sterile
• Sex organs do not mature

46
(No Transcript)
47
(No Transcript)
48

• 3) Altering Chromosome Structure
• usually occurs during cell division/ chromosome
  replication.
• Deletion removing a segment of chromosome
• ex. Cri du chat syndrome
• Duplication segments on a chromosome are
  repeated
• Inversion sections of the chromosome are
  reversed
• Translocation a segment of one chromosome is
  broken off and reattached on another
  non-homologous chromosome.

49
(No Transcript)
50

• GENOMIC IMPRINTING
• Genetic phenomenon by which certain genes are
  expressed in a parent-of-origin-specific
  manner.
• Inheritance process independent of classical
  Mendelian Inheritance.
• Involves methylation or silencing of genes as
  well as histone activation of others.
• VIDEO GHOST IN YOUR GENES

51
What is Prader-Willi syndrome?

• (PWS) is the most common known genetic cause of
  life-threatening obesity in children.
• abnormality on the 15th chromosome inherited from
  the father.
• It occurs in males and females equally and in all
  races.
• Prevalence estimates have ranged from 18,000 to
  125,000 with the most likely figure being
  115,000.
• PWS typically causes low muscle tone, short
  stature if not treated with growth hormone,
  incomplete sexual development, and a chronic
  feeling of hunger that, coupled with a metabolism
  that utilizes drastically fewer calories than
  normal, can lead to excessive eating and
  life-threatening obesity.
• Children with PWS have sweet and loving
  personalities, but this phase is also
  characterized by increased appetite, weight
  control issues, and motor development delays
  along with some behavior problems and unique
  medical issues.

52
Angelman Syndrome

• Genetic cause Abnormal maternal chromosome 15

53

• Prader

54
Figure 15.x1 Translocation
55
Figure 15.12 A tetraploid mammal?
56
Independent assortment of chromosomes and
crossing over produce genetic recombinants