Chapter 15 – chromosomal basis of inheritance - PowerPoint Presentation

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Chapter 15 – chromosomal basis of inheritance

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Chromosomal Theory of Inheritance

Theodor

Boveri

Walter Sutton

In 1902, Walter Sutton and Theodor

Boveri

developed the

Chromosome Theory of Inheritance. This theory basically states that Mendelian genes have a specific locus on the chromosome and that chromosomes undergo segregation and independent assortment during meiosis. This was a link between mitosis/ meiosis and Mendel’s findings.

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Thomas Hunt Morgan

Thomas Hunt Morgan was the first person to

associate a specific gene with a specific chromosome

. He worked with the common fruit fly (

Drosophila melanogaster

) and, after many generations, found a male fly with white eyes. From crosses with this organism, he discovered

sex-linkage

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Drosophila melanogaster

(Fruit Flies)

Morgan choose these organisms to do experiments on for several reasons:

- They are hardy

- Sex easily distinguishable

- Only 4 pairs of chromosomes

- Produce large numbers of offspring

- Can control matings - Traits that are easily observable - Can reproduce every 2 weeks4

Most observed phenotype is called

wild type

(ex. Red eyes). Alternate phenotypes are called

mutant phenotypes

(ex. White eyes)

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Sex Determination Systems

There are a few different systems of sex determination. They are:

- XY

- XO

- ZW

-

Haplo-diploid5

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X-Y Sex Determination System

The XY sex determination system occurs in mammals (including humans!); The

sex is determined by the sperm

; Females are XX and males are XY

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X-O Sex Determination System

The XO sex determination system occurs in grasshoppers, crickets, and most insects; There is only 1 type of sex chromosome; XX is female, and XO (only ONE X chromosome) is male;

Sperm cells carry either an X or no sex chromosome at all

.

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Z-W Sex Determination System

The ZW system of sex determination occurs in birds, some fish, and some insects; The

egg determines the sex

;

ZZ is male and ZW is female

…all sperm carry a Z and eggs have either a Z or a W

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Haplo-Diploid Sex Determination System

The

haplo

-diploid system of sex determination occurs in bees and ants. They do not have any sex chromosomes. Females develop from fertilized eggs (they are diploid), and males develop from unfertilized eggs (haploid)

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Chromosomal Basis of Sex

SRY Gene

The one gene that is on the Y chromosome and is very important is the

SRY gene (

Sex-determining Region of the Y). This makes males phenotypically male and instructs the gonads to develop into testes instead of ovaries. The

SRY

gene codes for a protein that regulates many other genes, triggering a cascade of biochemical, physiological, and anatomical features

. There is very LITTLE crossing over between the X and Y chromosomes because they are not homologous. 10

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Sex-Linkage

Sex linked genes generally mean genes found on the X chromosome. The human X chromosome contains about 1,100 genes. Because males and females inherit a different number of X chromosomes, the pattern of inheritance of X-linked genes differs from that of genes located on autosomes. Fathers can pass their genes onto all of their daughters and none of their sons (the sons get their Y chromosomes). Mothers can pass their traits onto both male and female children. In order for a son to get a recessive disorder, their mom must either be afflicted or a carrier of the gene.

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If an X-linked trait is due to a recessive allele, a

female

will express the phenotype only if she is homozygous for that allele.

Heterozygous females are carriers for the recessive trait.

Males would have the disorder if they only have one copy because they only have 1 X chromosome.

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Colorblindness

This is a disorder with seeing certain colors. There are various tests that can determine if someone is colorblind. There are different types of colorblindness. Red/ green colorblindness is one of the most common types.

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Duchenne

Muscular Dystrophy

Cross section of muscle shows extensive replacement of muscle fibers by adipose cells

Muscular Dystrophy is a sex-linked recessive disorder characterized by progressive skeletal muscle weakness, defects in muscle proteins (specifically

dystrophin

), and the death of muscle cells and tissue.

Duchenne

MD usually affects only males (females would need to have a father that also had the disease, but they usually do not live to reproduce) and is the most common of all the muscular dystrophies.

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Hemophilia

Hemophilia is a rare inherited disorder where the blood does not clot correctly. Afflicted people have little to none of a protein that is necessary for blood clotting. They can bleed internally (especially in the knees, elbows and ankles, and this can be fatal.

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In the 1800s, hemophilia was widespread among the royal families of Europe. Queen Victoria of England passed the allele to several of her descendants. Intermarriage with royal family members of other nations, such as Spain and Russia, further spread this X-linked trait.

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X-inactivation

In FEMALES, one X chromosome becomes almost completely inactivated in development and turns into a

Barr Body

. Most of the genes in the Barr Body are NOT expressed, although some are. Which X chromosome becomes inactivated is random, thus females become a mosaic of 2 types of cells. The X chromosome becomes inactivated by being

methylated

.

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Linked Genes

Linked genes are genes that are located on the same chromosome. They are usually inherited together. If they are NOT inherited together, it is due to crossing over. The results of crosses with linked genes do not follow normal Mendelian inheritance and are different from what would be expected according to the law of independent assortment.

Evidence

: Testcross

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Recombination

A recombinant is an offspring that has a different combination of traits than either of the parents.

The recombination frequencies can be used to make genetic linkage maps.

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Most of the offspring from the

Drosophila

testcross in Morgan’s experiment for

body color and

wing size had parental phenotypes. That suggested that the two genes (body color and wing size) were on the SAME chromosome, since the occurrence of parental types with a

frequency greater than 50% indicates that the genes are linked. About 17% of offspring, however, were recombinants.Morgan proposed that

some mechanism must occasionally break the physical connection between genes on the same chromosome.This process, called crossing over, accounts for the recombination of linked genes.

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Crossing over produces genetic recombination of linked genes

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Sturtevant

Sturtevant

Sturtevant

was a grad student that worked with Morgan on the flies. He discovered the

first method of gene mapping using the recombination frequencies

. The frequencies of recombination are used to determine the distance between genes on a chromosomes. Sturtevant predicted that

the farther apart two genes are, the higher the probability that a crossover will occur between them and, therefore, the higher the recombination frequency.

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Gene Mapping

Genetic Map

– ordered list of genes on a chromosome

Linkage Map

– genetic map based on recombination frequencies

1% recombination frequency = 1 map unit

Max value = 50%

If genes are greater than 50 map units apart, they behave as if they are on separate chromosomes (crossing over is almost certain to occur)20

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Nondisjunction/ Aneuploidy

Nondisjunction

– when chromosomes do not separate correctly during meiosis

Aneuploidy

– the term for an incorrect number of chromosomes; monosomy, trisomy, and polyploidy are all examples of aneuploidy

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Trisomy, Monosomy, Polyploidy

Trisomy

– having an extra copy of one chromosome; instead of having 2 copies you have 3; written as 2n + 1

Monosomy

– having only one copy of a certain chromosome, instead of the normal 2 copies; written as 2n - 1

Trisomy 18Monosomy 23

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Polyploidy

– having a whole extra set of chromosomes; Ex.

3N

or

4N

; common in plants; lethal in MOST animals although there are fish and amphibian

polyploid

species;

polyploids

are more nearly normal in phenotype than

aneuploids

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Alterations in Chromosome Structure

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Deletions

A deletion is when a piece of a chromosome is lost. This can be very bad because if that missing piece contains important genes, the phenotype of the afflicted person will be dramatically changed.

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Duplications

A duplication is when a section of a chromosome (a couple genes) is copied and included twice. This can greatly affect the individual. However, its usually not as bad as missing the genes all together (deletion).

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Inversion

An inversion occurs when a piece of a chromosome breaks off and reattaches in the wrong orientation. Because some genes are regulated by other genes near them, this can affect gene expression.

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Translocation

A translocation is when a piece of two chromosomes break off and attach to non-homologous chromosomes. It yields “recombinant” chromosomes.

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Duplications

and

translocations

are typically harmful. Reciprocal translocations or inversions can alter phenotype because a gene’s expression is influenced by its location among neighboring genes.

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Human Disorders due to Chromosomal Alterations

Although the frequency of

aneuploid

zygotes may be quite high in humans, most of these alterations are so disastrous to development that affected embryos are spontaneously aborted long before birth (miscarriage). There are several human disorders that are due to some type of chromosomal alteration



trisomy, monosomy, deletions, duplications, inversions, and translocations: - Down Syndrome

- Klinefelters Syndrome - Turners Syndrome - Cri du chat - CML (leukemia)

A baby with Down Syndrome28Males with an extra Y chromosome (

XYY

) tend to be somewhat taller than average.

Trisomy X (

XXX

), which occurs once in every 1,000 births live female births, produces healthy females.

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Down Syndrome – Trisomy 21

- Trisomy-21 (aneuploid condition)

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Although chromosome 21 is the smallest human chromosome, trisomy 21 severely alters an individual’s phenotype in specific ways. Individuals with Down syndrome have characteristic facial features, short stature, correctable heart defects, and developmental delays.

They are susceptible to respiratory infection, intellectual disability, and have an increased risk of developing leukemia and Alzheimer’s disease. All males and half of females with Down syndrome are sexually underdeveloped and sterile.

Trisomy 21 affects one in 700 children born in the United States. Most cases of Down syndrome result from nondisjunction during gamete production in one parent. The frequency of Down syndrome increases with the age of the mother. Trisomy 21 may be linked to some age-dependent abnormality in a meiosis I checkpoint that normally delays anaphase until all the kinetochores are attached to the spindle.

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Klinefelters

Syndrome - XXY

- XXY;

phenotypically

male- Male sex organs (but smaller); sterile- May have feminine characteristics- Usually have normal intelligence but may have slightly subnormal intelligence

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Turners Syndrome – XO (monosomy 23, monosomy X)

Genotype = XO

Monosomy 23

Aneuploid condition

Phenotypically female Sex organs don’t mature Sterile Intelligence is normal

Only known case of monosomy in humans

When given estrogen replacement therapy, girls with Turner syndrome develop secondary sex characteristics

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Cri du chat – Deletion in Chromosome #5

- Deletion in a part of Chromosome 5

These individuals have intellectual disability, small heads with unusual facial features, and have a cry like the mewing of a distressed cat

- Death in infancy or early childhood

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CML – Chronic

Myelogenous

Leukemia

CML is an acquired leukemia, resulting in a change in a person's DNA (NOT genetically inherited). This change results in an uncontrolled growth of white cells. This uncontrolled growth can bring about abdominal discomfort due to an enlarged spleen. Other symptoms may include excessive sweating (night sweats), weight loss, and an increased sensitivity to warm temperatures. 

This is due to an injury to the DNA that results in a shortened Chromosome 22.

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Genetic Imprinting

Genetic Imprinting is the phenomenon of the phenotype of the gene depends on whether it arrived via the egg or sperm.

Ex. Deletion in part of Chromosome 15…if it came from mom,

Angelman

; Dad =

Prader-Willi

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Prader-Willi

Syndrome

Due to imprinting

Deletion in chromosome 15

Allele from dad Intellectual disability Obesity Short stature

Unusually small hands and feet

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Angelman

Syndrome

- Due to imprinting

- Deletion in chromosome 15

- Allele from mom- Spontaneous laughter- Jerky movements, and other motor and mental symptoms

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Fragile-X Syndrome

Due to Imprinting

Abnormal X chromosome where the tip hangs on by a thread

- Intellectual disability if inherited from mom

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Extranuclear

genes exhibit a non-Mendelian pattern of inheritance

Extranuclear

or cytoplasmic genes are found in mitochondria and chloroplasts.

These organelles reproduce themselves and transmit their genes to daughter organelles.Organelle genes do not display Mendelian inheritance.Because a zygote inherits all its mitochondria from the ovum, all mitochondrial genes in most animals and plants demonstrate maternal inheritance.

Several rare human disorders are produced by mutations to mitochondrial DNA.These disorders primarily affect the ATP supply by producing defects in the electron transport chain or ATP synthase.

Other mitochondrial mutations may contribute to diabetes, heart disease, and other diseases of aging, such as Alzheimer’s disease.38