Human Genetics

Human GeneticsHuman

Genetics

Chapter 15: The Chromosomal Basis of Inheritance

Genes & ChromosomesGenes & Chromosomes

Mendel’s “hereditary factors” were genes, though this wasn’t known at the time

Today we can show that genes are located on

The location of a particular gene can be seen by tagging isolated chromosomes with a fluorescent dye that highlights the gene

Mendel’s “hereditary factors” were genes, though this wasn’t known at the time

Today we can show that genes are located on

The location of a particular gene can be seen by tagging isolated chromosomes with a fluorescent dye that highlights the gene

Chromosomal Theory of Inheritance

Chromosomal Theory of Inheritance

Mitosis and meiosis were first described in the late 1800s

The chromosome theory of inheritance states:

Mendelian genes have specific on chromosomes

Chromosomes undergo segregation and

The behavior of chromosomes during meiosis was said to account for Mendel’s laws of segregation and independent assortment

Mitosis and meiosis were first described in the late 1800s

The chromosome theory of inheritance states:

Mendelian genes have specific on chromosomes

Chromosomes undergo segregation and

The behavior of chromosomes during meiosis was said to account for Mendel’s laws of segregation and independent assortment

Experimental EvidenceExperimental EvidenceThe first solid evidence

associating a specific gene with a specific chromosome came from Thomas Hunt Morgan, an embryologist

Morgan’s experiments with fruit flies provided convincing evidence that chromosomes are the location of Mendel’s heritable factors

The first solid evidence associating a specific gene with a specific chromosome came from Thomas Hunt Morgan, an embryologist

Morgan’s experiments with fruit flies provided convincing evidence that chromosomes are the location of Mendel’s heritable factors

Experimental EvidenceExperimental EvidenceIn one experiment, Morgan

mated male flies with white eyes (mutant) with female flies with red eyes (wild type or normal)The F1 generation all had red

eyesThe F2 generation showed the

3:1 red:white eye ratio, but only males had white eyes

Morgan determined that the

Morgan’s finding supported the chromosome theory of inheritance

In one experiment, Morgan mated male flies with white eyes (mutant) with female flies with red eyes (wild type or normal)The F1 generation all had red

eyesThe F2 generation showed the

3:1 red:white eye ratio, but only males had white eyes

Morgan determined that the

Morgan’s finding supported the chromosome theory of inheritance

Sex linkageSex linkageSex chromosomes

determine gender of individualXX in females, XY in

malesEach ovum contains an X

chromosome, while a sperm may contain either an X or a Y chromosome

The on the Y chromosome codes for the development of testes

X chromosome has genes for many traits NOT associated with

Sex chromosomes determine gender of individualXX in females, XY in

malesEach ovum contains an X

chromosome, while a sperm may contain either an X or a Y chromosome

The on the Y chromosome codes for the development of testes

X chromosome has genes for many traits NOT associated with

Sex-linked InheritanceSex-linked InheritanceA gene located on either sex

chromosome is called a

In humans, sex-linked usually refers to a gene on the larger X chromosome

If gene is on Y chromosome Females don’t get Y-

linked traitsY-linked genes not

commonExample: Hairy ears

A gene located on either sex chromosome is called a

In humans, sex-linked usually refers to a gene on the larger X chromosome

If gene is on Y chromosome Females don’t get Y-

linked traitsY-linked genes not

commonExample: Hairy ears

X-linked InheritanceX-linked Inheritance

If gene is on X chromosomeCan inherit from

Sons always get

X chromosome from mom and Y chromosome from dad

If gene is on X chromosomeCan inherit from

Sons always get

X chromosome from mom and Y chromosome from dad

X-linked traitsX-linked traits

Color blindnessHemophiliaDuchene muscular dystrophy(SCID) Severe Combined

Immunodeficiency SyndromeAKA Bubble boy disease

Color blindnessHemophiliaDuchene muscular dystrophy(SCID) Severe Combined

Immunodeficiency SyndromeAKA Bubble boy disease

X-linked recessive genes

X-linked recessive genes

Sex-linked genes follow specific patterns of inheritance

For a recessive sex-linked trait to be expressedA female needs

of the alleleA male needs only of

the alleleSex-linked recessive

disorders are much more common in males than in females

Sex-linked genes follow specific patterns of inheritance

For a recessive sex-linked trait to be expressedA female needs

of the alleleA male needs only of

the alleleSex-linked recessive

disorders are much more common in males than in females

Females & X-linkedFemales & X-linked

In mammalian females, one of the two X chromosomes in each cell is randomly inactivated during embryonic development

The inactive X condenses into a

If a female is heterozygous for a particular gene located on the X chromosome, she will be a mosaic for that character

In mammalian females, one of the two X chromosomes in each cell is randomly inactivated during embryonic development

The inactive X condenses into a

If a female is heterozygous for a particular gene located on the X chromosome, she will be a mosaic for that character

CarriersCarriersFemales can be carriers

Other X has normal dominant gene

Males cannot be carriers, they either have it or they do notMales will give gene to all

daughters, none to sonsIf he has the gene all his

daughters will be carriers of trait

Females can be carriers

Other X has normal dominant gene

Males cannot be carriers, they either have it or they do notMales will give gene to all

daughters, none to sonsIf he has the gene all his

daughters will be carriers of trait

Red-green color blindness

Red-green color blindness

X-linked disorderCan’t differentiate these two

colorsMany people who have this are

not aware of the factFirst described in a boy who

could not be trained to harvest only the ripe, red apples from his father’s orchard. Instead, he chose green apples

as often as he chose redWhat serious consequence could

result from this?

X-linked disorderCan’t differentiate these two

colorsMany people who have this are

not aware of the factFirst described in a boy who

could not be trained to harvest only the ripe, red apples from his father’s orchard. Instead, he chose green apples

as often as he chose redWhat serious consequence could

result from this?

Sex-Linked Traits:

 1. Normal Color Vision: A: 29,  B: 45,  C: --,  D: 26

 2. Red-Green Color-Blind: A: 70,  B: --,  C: 5,  D: --

 3. Red Color-blind: A: 70,  B: --,  C: 5,  D: 6

 4. Green Color-Blind: A: 70,  B: --,  C: 5,  D: 2

HemophiliaHemophiliaAn X-linked disorder that

causes a problem with

If your blood didn’t have the ability to clot and you bruised yourself or scraped your knee, you would be in danger of bleeding to death

Queen Victoria was a carrier and she passed the trait on to some of her children

An X-linked disorder that causes a problem with

If your blood didn’t have the ability to clot and you bruised yourself or scraped your knee, you would be in danger of bleeding to death

Queen Victoria was a carrier and she passed the trait on to some of her children

HemophiliaHemophilia

About 1 in every 10,000 males has hemophilia, but only about 1 in every 1 million females inherits the same disorder

Why????Males only have one X chromosome

A single recessive allele for hemophilia will cause the disorder

Females would need two recessive alleles to inherit hemophilia

Males inherit the allele for hemophilia on the X chromosome from their carrier or infected mothers

About 1 in every 10,000 males has hemophilia, but only about 1 in every 1 million females inherits the same disorder

Why????Males only have one X chromosome

A single recessive allele for hemophilia will cause the disorder

Females would need two recessive alleles to inherit hemophilia

Males inherit the allele for hemophilia on the X chromosome from their carrier or infected mothers

HemophiliaHemophilia

HemophiliaHemophiliaHemophilia can be treated

with and injections of Factor VIII, the blood-clotting enzyme that is absent in people affected by the condition

Both treatments are expensive

New methods of DNA technology are being used to develop a safer and cheaper source of the clotting factor

Hemophilia can be treated with and injections of Factor VIII, the blood-clotting enzyme that is absent in people affected by the condition

Both treatments are expensive

New methods of DNA technology are being used to develop a safer and cheaper source of the clotting factor

Sex-linked QuestionsSex-linked Questions Both the mother and the father of a male

hemophiliac appear normal. From whom did the son inherit the allele for hemophilia? What are the genotypes of the mother, the father and the son?

A woman is color blind. If she marries a man with normal vision, what are the chances that her daughter will be color blind? Will be carriers? What are her chances that her sons will be color blind?

Is it possible for two normal parents to have a color blind daughter?

Both the mother and the father of a male hemophiliac appear normal. From whom did the son inherit the allele for hemophilia? What are the genotypes of the mother, the father and the son?

A woman is color blind. If she marries a man with normal vision, what are the chances that her daughter will be color blind? Will be carriers? What are her chances that her sons will be color blind?

Is it possible for two normal parents to have a color blind daughter?

What is on our chromosomes?What is on our chromosomes?

Each chromosome has hundreds or thousands of genesGenes located on the same chromosome that tend to

be inherited together are called Thomas Morgan found that body color and wing size of

fruit flies are usually inherited together in specific combinations

He noted that these genes do not assort independently, and reasoned that they were on the same chromosome

However, nonparental phenotypes were also producedUnderstanding this result involves exploring genetic

recombination

Each chromosome has hundreds or thousands of genesGenes located on the same chromosome that tend to

be inherited together are called Thomas Morgan found that body color and wing size of

fruit flies are usually inherited together in specific combinations

He noted that these genes do not assort independently, and reasoned that they were on the same chromosome

However, nonparental phenotypes were also producedUnderstanding this result involves exploring genetic

recombination

Genetic RecombinationGenetic Recombination

Mendel observed that combinations of traits in some offspring differ from either parent

Offspring with a phenotype matching one of the parental phenotypes are called

Offspring with nonparental phenotypes (new combinations of traits) are called

Morgan discovered that genes can be linked, but the linkage was incomplete, as evident from recombinant phenotypesMorgan proposed that some process must

sometimes break the physical connection between genes on the same chromosome

Mechanism was the of homologous chromosomes

Mendel observed that combinations of traits in some offspring differ from either parent

Offspring with a phenotype matching one of the parental phenotypes are called

Offspring with nonparental phenotypes (new combinations of traits) are called

Morgan discovered that genes can be linked, but the linkage was incomplete, as evident from recombinant phenotypesMorgan proposed that some process must

sometimes break the physical connection between genes on the same chromosome

Mechanism was the of homologous chromosomes

Genetic mapGenetic map

Alfred Sturtevant, one of Morgan’s students, constructed a

, an ordered list of the genetic loci along a particular chromosome

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

Alfred Sturtevant, one of Morgan’s students, constructed a

, an ordered list of the genetic loci along a particular chromosome

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

Genetic mapGenetic mapA is a genetic map

of a chromosome based on recombination frequencies

Distances between genes can be expressed as map units; one map unit, or centimorgan, represents a 1% recombination frequency (max value = 50%)

Map units indicate relative distance and order, not precise locations of genes

A is a genetic map of a chromosome based on recombination frequencies

Distances between genes can be expressed as map units; one map unit, or centimorgan, represents a 1% recombination frequency (max value = 50%)

Map units indicate relative distance and order, not precise locations of genes

Human Genome Project

Human Genome Project

The most ambitious mapping project to date has been the sequencing of the human genome

Officially begun as the Human Genome Project in 1990, the sequencing was largely completed by 2003

The project had three stages:

Genetic (or linkage) mapping

Physical mapping

DNA sequencing

The most ambitious mapping project to date has been the sequencing of the human genome

Officially begun as the Human Genome Project in 1990, the sequencing was largely completed by 2003

The project had three stages:

Genetic (or linkage) mapping

Physical mapping

DNA sequencing

Human Genome Project

Human Genome Project

A expresses the distance between genetic markers, usually as the number of base pairs along the DNA

It is constructed by cutting a DNA molecule into many short fragments and arranging them in order by identifying overlaps

Sequencing was then done on the chromosomes

A expresses the distance between genetic markers, usually as the number of base pairs along the DNA

It is constructed by cutting a DNA molecule into many short fragments and arranging them in order by identifying overlaps

Sequencing was then done on the chromosomes

Gene ManipulationGene ManipulationDNA sequencing has depended

on advances in technology, starting with making recombinant DNA

In recombinant DNA, nucleotide sequences from two different sources,

, are combined in vitro into the same DNA molecule

Methods for making recombinant DNA are central to

, the direct manipulation of genes for practical purposes

DNA sequencing has depended on advances in technology, starting with making recombinant DNA

In recombinant DNA, nucleotide sequences from two different sources,

, are combined in vitro into the same DNA molecule

Methods for making recombinant DNA are central to

, the direct manipulation of genes for practical purposes

BiotechnologyBiotechnology

DNA technology has revolutionized biotechnology,

One benefit of DNA technology is identification of human genes in which mutation plays a role in genetic diseases

Scientists can diagnose many human genetic disorders by using molecular biology techniques to look for the disease-causing mutation

Genetic disorders can also be tested for using genetic markers that are linked to the disease-causing allele

DNA technology has revolutionized biotechnology,

One benefit of DNA technology is identification of human genes in which mutation plays a role in genetic diseases

Scientists can diagnose many human genetic disorders by using molecular biology techniques to look for the disease-causing mutation

Genetic disorders can also be tested for using genetic markers that are linked to the disease-causing allele

TransgenicsTransgenicsAdvances in DNA technology and genetic

research are important to the development of new drugs to treat diseases

Transgenic animals are made by introducing genes from Transgenic animals are pharmaceutical

“factories,” producers of large amounts of otherwise rare substances for medical use

“Pharm” plants are also being developed to make human proteins for medical use

This is useful for the production of insulin, human growth hormones, and vaccines

Advances in DNA technology and genetic research are important to the development of new drugs to treat diseases

Transgenic animals are made by introducing genes from Transgenic animals are pharmaceutical

“factories,” producers of large amounts of otherwise rare substances for medical use

“Pharm” plants are also being developed to make human proteins for medical use

This is useful for the production of insulin, human growth hormones, and vaccines

Gene TherapyGene Therapy

Gene therapy is the

Gene therapy holds great potential for treating disorders traceable to a single defective gene

Vectors are used for delivery of genes into specific types of cells (example = bone marrow)

Gene therapy raises ethical questions, such as whether human germ-line cells should be treated to correct the defect in future generations

Gene therapy is the

Gene therapy holds great potential for treating disorders traceable to a single defective gene

Vectors are used for delivery of genes into specific types of cells (example = bone marrow)

Gene therapy raises ethical questions, such as whether human germ-line cells should be treated to correct the defect in future generations

Causes of Genetic Disorders

Causes of Genetic Disorders

Meiosis usually functions accurately, but problems may arise at times

Large-scale chromosomal alterations often lead to or cause a

variety of developmental disordersIn , pairs of homologous

chromosomes do not separate normally during meiosisMay occur in Meiosis I or IIOne gamete receives two of the same type of

chromosomeAnother gamete receives no copy of the

chromosome

Meiosis usually functions accurately, but problems may arise at times

Large-scale chromosomal alterations often lead to or cause a

variety of developmental disordersIn , pairs of homologous

chromosomes do not separate normally during meiosisMay occur in Meiosis I or IIOne gamete receives two of the same type of

chromosomeAnother gamete receives no copy of the

chromosome

Fertilization after nondisjunction

Fertilization after nondisjunction

Nondisjunction results in gametes with an

If the other gamete is normal, the zygote will have 2n + 1 (47 in humans) or 2n - 1 (45 in humans)

Most of the time an extra chromosome prevents development from occurring

results from the fertilization of gametes in which nondisjunction occurred

Offspring with this condition have an abnormal number of a particular chromosome

Nondisjunction results in gametes with an

If the other gamete is normal, the zygote will have 2n + 1 (47 in humans) or 2n - 1 (45 in humans)

Most of the time an extra chromosome prevents development from occurring

results from the fertilization of gametes in which nondisjunction occurred

Offspring with this condition have an abnormal number of a particular chromosome

Fertilization after nondisjunction

Fertilization after nondisjunction

occurs when the zygote has only one copy of a particular chromosome (2n -1)

occurs when the zygote has three copies of a particular chromosome (2n+1)

is a condition in which an organism has more than two complete sets of chromosomesTriploidy (3n) is three sets of chromosomesTetraploidy (4n) is four sets of chromosomes

Polyploidy is common in plants, but not animalsPolyploids are more normal in appearance than

aneuploids

occurs when the zygote has only one copy of a particular chromosome (2n -1)

occurs when the zygote has three copies of a particular chromosome (2n+1)

is a condition in which an organism has more than two complete sets of chromosomesTriploidy (3n) is three sets of chromosomesTetraploidy (4n) is four sets of chromosomes

Polyploidy is common in plants, but not animalsPolyploids are more normal in appearance than

aneuploids

Nondisjunction animationAnimation #2

Human Disorders due to chromosome alterationsHuman Disorders due to chromosome alterations

Alterations of chromosome number are associated with some serious disorders

Some types of aneuploidy appear to upset the genetic balance less than others, resulting in individuals surviving to birth and beyond

These surviving individuals have a set of symptoms, or syndrome, characteristic of the type of aneuploidy

Alterations of chromosome number are associated with some serious disorders

Some types of aneuploidy appear to upset the genetic balance less than others, resulting in individuals surviving to birth and beyond

These surviving individuals have a set of symptoms, or syndrome, characteristic of the type of aneuploidy

Down SyndromeDown SyndromeDown syndrome is an

aneuploid condition that results from three copies of chromosome 21

Most common serious birth defect

1 in 700 birthsVarying degrees of mental

retardationDue to Gart gene on 21st

chromosome1/2 eggs of female will

carry extra 21 and 1/2 will be normal

Risk increases with

Down syndrome is an aneuploid condition that results from three copies of chromosome 21

Most common serious birth defect

1 in 700 birthsVarying degrees of mental

retardationDue to Gart gene on 21st

chromosome1/2 eggs of female will

carry extra 21 and 1/2 will be normal

Risk increases with

Incidence of Down Syndrome

Incidence of Down Syndrome

Klinefelter SyndromeKlinefelter Syndrome

Klinefelter syndrome is the result of an extra X chromosome in a male, producing XXY individuals

1 in every 2,000 birthsCould be from

nondisjunction in either parent

Klinefelter syndrome is the result of an extra X chromosome in a male, producing XXY individuals

1 in every 2,000 birthsCould be from

nondisjunction in either parent

Turner SyndromeTurner Syndrome

Turner syndrome produces XO females, who are sterile

1 in every 5,000 birthsIt is the only known

viable monosomy in humans

Girls with Turner Syndrome do not develop secondary sex characteristics such as breast tissue and underarm or pubic hair

Turner syndrome produces XO females, who are sterile

1 in every 5,000 birthsIt is the only known

viable monosomy in humans

Girls with Turner Syndrome do not develop secondary sex characteristics such as breast tissue and underarm or pubic hair

Mutation typesMutation typesAlterations of chromosome structure may

also lead to genetic disordersBreakage of a chromosome can lead to

four types of changes in chromosome structure: removes a chromosomal

segment repeats a chromosomal segment reverses a segment within a

chromosome moves a segment from one

chromosome to another

Alterations of chromosome structure may also lead to genetic disorders

Breakage of a chromosome can lead to four types of changes in chromosome structure: removes a chromosomal

segment repeats a chromosomal segment reverses a segment within a

chromosome moves a segment from one

chromosome to another

Mutation typesMutation types

Cri du chatCri du chat

The syndrome cri du chat (“cry of the cat”), results from a specific deletion in chromosome 5

A child born with this syndrome is mentally retarded and has a catlike cry

Individuals usually die in infancy or early childhood

The syndrome cri du chat (“cry of the cat”), results from a specific deletion in chromosome 5

A child born with this syndrome is mentally retarded and has a catlike cry

Individuals usually die in infancy or early childhood

Chronic Myelogenous Leukemia

Chronic Myelogenous Leukemia

Certain cancers, including chronic myelogenous leukemia (CML), are caused by translocations of chromosomes

Occurs with the exchange of a large portion of chromosome 22 with a small fragment from the tip of chromosome 9

Shortened, easily recognizable chromosome 22 is called the

Certain cancers, including chronic myelogenous leukemia (CML), are caused by translocations of chromosomes

Occurs with the exchange of a large portion of chromosome 22 with a small fragment from the tip of chromosome 9

Shortened, easily recognizable chromosome 22 is called the

Genomic imprintingGenomic imprintingThere are two normal exceptions to Mendelian

geneticsOne exception involves genes located in the

nucleus, and the other exception involves genes located outside the nucleusGenes marked in gametes as coming from mom

or dadGenes inherited from father expressed

differently than genes inherited from motherFor a small fraction of mammalian traits, the

phenotype depends on which parent passed along the alleles for those traits

Such variation in phenotype is called

Example = Insulin-like growth factor in mice

There are two normal exceptions to Mendelian genetics

One exception involves genes located in the nucleus, and the other exception involves genes located outside the nucleusGenes marked in gametes as coming from mom

or dadGenes inherited from father expressed

differently than genes inherited from motherFor a small fraction of mammalian traits, the

phenotype depends on which parent passed along the alleles for those traits

Such variation in phenotype is called

Example = Insulin-like growth factor in mice

Organelle genes Organelle genes Extranuclear genes

(or cytoplasmic genes) are genes found in organelles in the cytoplasm

Mitochondria, chloroplasts, and other plant plastids carry small circular DNA molecules

Extranuclear genes are inherited

because the zygote’s cytoplasm comes from the egg

Extranuclear genes (or cytoplasmic genes) are genes found in organelles in the cytoplasm

Mitochondria, chloroplasts, and other plant plastids carry small circular DNA molecules

Extranuclear genes are inherited

because the zygote’s cytoplasm comes from the egg

Organelle genes Organelle genes The first evidence of

extranuclear genes came from studies on the inheritance of yellow or white patches on leaves of an otherwise green plant

Some defects in mitochondrial genes prevent cells from making enough ATP and result in diseases that affect the muscular and nervous systems For example, mitochondrial

myopathy and Leber’s hereditary optic neuropathy

The first evidence of extranuclear genes came from studies on the inheritance of yellow or white patches on leaves of an otherwise green plant

Some defects in mitochondrial genes prevent cells from making enough ATP and result in diseases that affect the muscular and nervous systems For example, mitochondrial

myopathy and Leber’s hereditary optic neuropathy

Review QuestionsReview Questions1. State the 2 basic ideas behind the chromosomal theory of

inheritance.2. Explain Morgan’s experiment and how it gave evidence that

genes are located on chromosomes.3. Explain sex linkage and sex-linked inheritance.4. Name and describe characteristics of 4 genetic diseases

that are known to be X-linked.5. Explain the idea of a “carrier” for an X-linked genetic

disease.6. Carry out a monohybrid cross of an X-linked trait using a

Punnett square.7. Explain the idea of linked genes.8. Explain the result of genetic recombination.9. Identify the significance of genetic maps and linkage maps10. Describe the Human Genome Project and differentiate

between its 3 main stages.11. Discuss the advantages of gene manipulation and

biotechnology.12. Describe various uses of transgenic animals.13. Explain the purpose and use of gene therapy.14. Explain how errors in meiosis can cause genetic syndromes.

Review QuestionsReview Questions15. Define nondisjunction.16. Differentiate between aneuploidy, monosomy, trisomy, and

polyploidy.17. Explain the cause, frequency, and problems associated with

the following genetic syndromes: Down syndrome, Klinefelter syndrome, & Turner syndrome.

18. Describe the effect of mutations on genes.19. Differentiate between deletion, duplication, inversion, and

translocation mutations.20. Explain cri du chat syndrome.21. Explain chronic myelogenous leukemia as an example of a

disease-causing mutation.22. Explain genomic imprinting and the effects of extranuclear

genes.