Chapter 14Human Genetics

Introduction

Scientists know much less about human inheritance than they do about other organisms.

Model organisms are the fruit fly and mice.

With this new understanding, scientists must study genetics carefully. WHY?

Human Chromosomes In each of our somatic cells, we have 44

autosomes and 2 sex chromosomes (23 pairs of chromosomes)

In order to study our chromosomes, biologists photograph cells when they are in mitosis (metaphase).

A karyotype is a picture of the chromosomes when they are grouped together in pairs.

Normal females have 46,XX notation and normal males have 46,XY notation.

A normal egg cell is 23,X. A normal sperm cell is either 23,X or 23,Y.

Karyotypes1. Cells are grown (in a cell culture dish) to increase their number.2. Cell division is then stopped in metaphase. (Why metaphase?)3. Cells are centrifuged and lysed to release chromosomes.4. Chromosomes are stained, photographed, and grouped by size

and banding patterns.“p” = shorter arm above centromere “q” = longer arm below centromere

How is gender determined?

A normal egg cell is 23,X. A normal sperm cell is either 23,X or 23,Y.

Gender is determined by inheritance of either XX or XY. So, we can say that the male determines the sex of a child.

Genetic differences (3:52)

Pedigrees A pedigree chart is used to show how

a trait is passed from one generation to the next.

In a pedigree, a circle represents a female and a square represents a male.

A colored square or circle means that person has the trait, while a non-colored square or circle means that person does not have the trait.

Pedigrees

Genes and the Environment Some of the most obvious traits are

impossible to trace to a single gene. This is due to two main reasons:1. They are polygenic.2. Many traits are influenced by the environment. For example, improved health practices since the 1800s in the U.S. has caused greater height.

Environmental effects are not inherited.

Human Genes Our complete set of

genetic information is called the human genome.

Studying the human genome has taken much longer than other organisms because humans have a long generation time, complex life cycle, and produce few offspring.

Genes and Disorders For many disorders scientists do not know the

link between DNA and the disorder. The link for cystic fibrosis and sickle cell disease

is understood The small change in the DNA of one gene

affects the structure of a protein – this causes the disorder.Lysosomal Disease (2:09)

What makes an allele dominant or recessive?

Depends on the gene’s protein product and its role in the cell

Cystic fibrosis – one copy of the normal allele provides enough proteins to function Normal allele is dominant

over the recessive Huntington’s – one copy

of the normal allele is not enough, so the disorder allele is dominant over the normal allele

Sex-linked Genes

Y chromosome is smaller than the X, therefore it has

fewer genes. Males have only one X chromosome, so all X-

linked alleles are expressed in males

If a disorder is recessive, females must have two copies of the allele because they have two X chromosomes.

Sex-linked Genetic Disorders

Sex-linked Genetic Disorders

Colorblindness: far more common in males Said to be X-linked, meaning that the allele

is only present on the X chromosome Since males only have one X chromosome,

they only need one copy of the recessive allele to have colorblindness, whereas females need two copies.

Hemophilia, Duchenne muscular dystrophy

Sex-linked Punnett Square

Does Dad have the disease?

What about Mom?

Probability that a daughter will inherit?

Probability that a son will inherit?

X-chromosome Inactivation

Females need to adjust to the extra X allele.

British geneticist Mary Lyon discovered that one X chromosome is randomly switched off.

The switched off chromosome forms a dense region in the nucleus called the Barr body.

Normally not found in males Reason for color in calico cats

Chromosomal Disorder In meiosis, chromosomes separate.

If this fails to work properly, errors occur Nondisjunction – most common error

When homologous chromosomes fail to separate

Abnormal number of chromosomes finds its way into gametes

Trisomy 13, 18, and 21

Human Chromosomal Disorders: Trisomy 13, 18, and 21

Trisomy 21 - Down Syndrome (47,XY,+21)

Trisomy 13 – Patau Syndrome (47,XY,+13)

Trisomy 18 – Edward’s Syndrome (47,XY,+18)

Almost every organ system affected; 1:6000 live births. Children with full Trisomy 18 generally do not live more than a few months.

Serious eye, brain, circulatory defects as well as cleft palate; 1:15,000 live births; children rarely live more than a few months

Human Chromosomal Disorders: Nondisjunction of sex chromosomes

Klinefelter Syndrome (47,XXY)Male sex organs present, but sterile; breast enlargement and other feminine body characteristics; normal intelligence; 1:750 live male births

47,XYY Somewhat taller than average and often have below normal intelligence; at one time (~1970s), it was thought that these men were likely to be criminally aggressive, but this hypothesis has been proven false; 1:1000 live male births

Human Chromosomal Disorders: Nondisjunction of sex chromosomes

Trisomy X 47,XXX 1:1000 live female births; healthy and fertile; often cannot be distinguished from normal female except by karyotype

Turner’s Syndrome (45,XO)1:2500 live female births; do not mature sexually during puberty and are sterile; short stature and normal intelligence

Genetic Engineering Until recently we could

not modify the genetic code (genome).

Scientists use their knowledge of the structural and chemical properties of DNA to study and change it

We have the technology to extract DNA from cells, to cut DNA into smaller pieces, and to identify the sequence of bases

DNA Fingerprinting No two individuals are exactly genetically alike. DNA fingerprinting analyzes sections of DNA that

vary widely from person to person DNA separated into series of bands Useful in convictions (first used in England, 1986) Samples can be taken from blood, hair, and

bodily fluidsIt’s easy to see in this example that daughter 2 is the child from the mother’s previous marriage and son 2 is adopted. You can see that both daughter 1 and son 1 share RFLPs with both the mom and dad, while daughter 2 has RFLPs of the mom but not the dad, and son 2 does not have RFLPs from either parent, so he must have been _____.Fingerprinting FUN!

The Human Genome Project Sequencing of the entire human genome Started in 1990 and finished in 2003 Cost to American taxpayers? $3.8 billion Project goals:

Identify all the approximately 20,000-25,000 genes in human DNA and determine the sequences of the 3.1 billion base pairs that make up human DNA

Store this information in databases Improve tools for data analysis Transfer related technologies to the private

sector Address the ethical, legal, and social issues

(ELSI) that may arise from the project. Genome Video (24:20)

DNA Extraction How do we get DNA out of cells? Three basic steps:

Break cells open and remove the membranes

Remove proteins from the DNA using salt Add ethanol – DNA is not soluble in ethanol

so it clumps together

Gene TherapyGene Therapy: An absent or faulty gene is

replaced by a normal working one. How does it work?

1. Body cells with the defective gene are isolated2. A copy of the normal gene is inserted into viruses3. The isolated cells are "infected" with these modified viruses4. The viral DNA which carries the normal gene inserts itself into the host DNA5. The host cells that now contain the new DNA are cloned in the lab6. These new cultured cells are injected into the patient

Gene Therapy

Success of Gene Therapy

When has it been successful? Scientists have seen some success in the

following:▪ Inherited blindness▪ Sickle cell disease▪ Cystic fibrosis▪ Some cancers (leukemia, lymphoma,

myeloma)▪ Parkinson’s disease▪ Huntington’s disease▪ SCID (severe combined immunodeficiency)▪ Deafness in guinea pigs

Gene Therapy Limitations Limitations & Problems

1. The treatment may only be temporary2. Patient has an immune response to the virus3. Virus may regain its ability to cause disease4. The therapy must target specific cells5. Usually cannot reverse damage already done to body systems6. The cost for just one treatment can be well over $100,000 (and insurance doesn’t cover it)

Gene Therapy Success (3:34)What is Gene Therapy? (15:27) This one might hurt

your brain!