Chapter 14Human Heredity

14-1 Human Heredity

• Scientists once knew much less about humans then about other “model” organisms such as fruit flies and mice

• With the completion of the Human Genome Project scientists are on verge of understanding human genetics at least as well as they understand that of some other organisms

Human Chromosomes• To analyze chromosomes, cell

biologists photograph cells in mitosis

• Chromosomes are fully condensed and easiest to see during metaphase

Karyotype• A picture of chromosomes

arranged in order

• We all began life when a haploid sperm fertilized a haploid egg carrying just ________ chromosomes each.

• The _________________________ zygote or fertilized egg contained the full complement of __________ chromosomes

23

Diploid

46

Sex Chromosomes• Determine an individuals sex

Females: XX

Males: XY

• The regular 44 chromosomes are known as autosomes

Q: Why are males & females born in a roughly 50:50 ratio?

A: All egg cells carry a single _______ chromosome. However, half of all sperm carry an _______ chromosome, the other half carry a ________ chromosome

XX

Y

Human Traits• In order to apply Mendelian

genetics to humans, biologists must identify an inherited trait controlled by a single gene

• Then, they have to study how the trait is passed from one generation to the next

Pedigree• A chart which shows the

relationship within a family

• Most human traits are not coded for by single genes

• Also, many traits are strongly influenced by environmental factors–Ex.) average height has

increased 10cm in the United States and Europe since 1800’s

Polygenic Traits• Traits coded for by many genes

• Ex.) skin color, hair color

The Human Genome• Our complete set of genetic

information

• Includes tens of thousands of genes

• Until recently the identification of a human gene took years of work

• Long generation times

• Complex life cycle

• Produce few offspring

Humans aren’t easy test subjects

Blood Group Genes• A number of genes are responsible

for human blood groups, but the best known are the ABO and Rh blood groups

• Rh blood groups

• Rh+ (dominant)

• Rh- (recessive)

Q: How do scientists identify recessive alleles that cause these disorders

A: Compare affected persons genotype to normal persons

PKU – phenylketonuria • Lack enzyme needed to break down

phenylalanine• Found in milk and other foods• If newborn has PKU, phenylalanine may build

up in the tissues during severe mental retardation

• If newborns are tested early, they can be placed on a low phenylalanine diet which prevents most of the affects

• PKU is caused by a recessive allele carried on chromosome 12

PKU

Tay Sachs• Autosomal recessive• Found mostly in Jewish families of

central and eastern European ancestry• Results in nervous system breakdown

and death in the first few years of life• There is no treatment, but there is a

test prospective parents can take

Achondroplasia - dwarfism

• Never reach 4 feet 4 inches

• Cartilage forms in such a way that the arms and legs end up being disproportionately short

• 1 in every 10,000 is affected

Huntington's• Progressive loss of muscle

control and mental function until death occurs

• People with disease show no symptoms until they are in their 30’s and 40’s

Huntington's affect on the brain

Codominant• Sickle cell disease

• Affects 1 in 500 African Americans

From Gene to Molecule

Cystic Fibrosis (CF)• Most common among people whose

ancestors come from northern Europe

• Caused by a recessive allele on chromosome 7

• Produce a thick heavy mucus that clogs their lungs and breathing passageways

• Serious digestive problems

• Only half survive into their 20’s

Sickle Cell Disease• Characterized by the bent and twisted shape of

the red blood cell• Sickle shaped red blood cell tend to get stuck in

the capillaries• Produce physical weakness and damage to the

brain, heart and spleen• Sometimes fatal• Change in just one DNA base• This change inserts amino acid valine in place of

glutamic acid• Hemoglobin molecules stick together and form

long chains that produce the characteristic shape of sickled cells

Q: Why do so many African Americans carry the sickle cell allele?

• A: Many African Americans have West Central African ancestry where malaria is a serious problem

• People who are heterozygous for the sickle cell allele don’t get sickle cell and they don’t get malaria

Where malaria is common Where sickle cell is common

Dominant or Recessive• It all depends on the nature of a

genes protein product and its role in the cell

• Ex.) In CF, one copy of the normal allele can supply cells with enough chloride channel proteins to function therefore the normal CF allele is considered ____________________Dominant

14-2 Human Chromosomes

• A human diploid cell contains more than 6 billion nucleiotide pairs of DNA

• Despite its size, all of this information is neatly packed into the 46 chromosomes present in every diploid cell

• Each chromosome is like a library containing hundreds or even thousands of books

• Biologists are many decades away from mastering the contents of these books, but they are learning just how many books there are and what they deal with

Sex Linked Genes

• Genes located on the sex chromosomes

• Most found on the ________ chromosomeX

Colorblindness• Gene associated with color vision

are located on the X chromosome

• Affects 1 in 10 males

• Affects 1 in 100 females

Q: Why the difference between the sexes?

A: Males have ____________________________ X chromosome. Thus, all X-linked alleles are expressed in males, even if they are recessive

• In order for a woman to be affected, there must be __________________________ of the allele

just one

Two copies

Hemophilia• A protein necessary for normal

______________________________is missing

• 1 in 10,000 males• People with hemophilia can bleed to

death from minor cuts and may suffer from internal bleeding

• Treated with normal clotting factors

Blood clotting

Duchenne Muscular Dystrophy

• Results in progressive weakening and loss of skeletal muscle

• Rarely live past early adulthood

• In the U.S. 1 in 3000 males is born with Duchenne muscular dystrophy

• Caused by a defective version of the gene that codes for a muscle protein

X-Chromosome Inactivation

Q: If all you need is one X chromosome, what happens to the extra X chromosome in females?

A: one chromosome is randomly switched off

• Forms a barr body – dense region in the nucleus

Calico Cats• Fur color is on the X chromosome. Some

areas have one color switched on, and others its switched off

nondisjunction• When homologous chromosomes

fail to separate – most common error in meiosis

• If nondisjunction occurs, abnormal numbers of chromosomes may find their way into gametes

Down Syndrome• When nondisjunction happens and a

baby is born with 3 copies of chromosome 21

• Trisomy 21

• 1 in 800 in U.S.

• Mild to severe retardation

• Susceptible to many diseases

• Increased frequency of birth defects

Down Syndrome

Turners Syndrome (female)

• Only inherit one X chromosome, and no Y

• Genotype = XO

• Women with Turner syndrome are sterile, their sex organs don’t properly develop at puberty

Klinefelters Syndrome (males)

• Inherit extra X chromosomes• Genotype = XXY• The extra X interferes with meiosis and

usually prevents them from reproducing• Some cases XXXY or XXXXY• These abnormalities show us the role of Y in

sex determination– Even in combination with several X’s, the Y

makes them male• But if this Y is absent, the embryo develops

into a female

14-3 Human Molecular Genetics

Human DNA Analysis• Way too much DNA to search

through

• Biologists search the volumes of the human genome using DNA sequences

Testing for alleles• If two prospective parents suspect

they might be carrying recessive alleles for a genetic disorder they can now get a test to determine the risk of passing that trait on to their children– Use labeled DNA probes to detect

specific sequences found in disease causing alleles

– Looking at changes in restrictive enzyme cutting sites

– Looking at differences in lengths of alleles

DNA fingerprinting• Analyzes sections of DNA that

have little or no known function but vary widely from one individual to another

• Used to settle paternity disputes

• Convict criminals and overturn convictions

The Human Genome Project• Advances in DNA sequencing technologies at the close

of the twentieth century made it possible to begin sequencing entire genomes

• At first, biologists worked on small genomes of viruses and bacteria

• In 1990, scientists in the United States and other countries began the Human Genome Project– An attempt to sequence all human DNA

• In 2000 scientists announced that the DNA sequence of the human genome was essentially complete

• We estimate as little as 31,000 genes– Fruit fly – 14,000– C. elegans worm 20,000

• Now the task is to figure out how so few genes make an organism as complex as us

Promoter• Section of DNA that signals the start of

a gene• Researchers are looking for genes

that provide useful clues to some of the basic properties of life

• Also looking for genetic information that may be useful in developing new drugs and treatment of disease

A Breakthrough for Everyone

• Data from the human genome project is posted on the internet on a daily basis

• www.genome.gov

Gene Therapy• Replacing an absent or faulty

gene by a normal working gene

Ethical Issues in Human Genetics

• There are many questions which science will rapidly force society to come to grips with

• If it’s just as easy to manipulate genes for personal preference then it is to cure a disease should we do it?

• Our society will have to develop a thoughtful and ethical conscious of what should and shouldn’t be done with the human genome