Chapter 14Chapter 14 The Human Genome The Human Genome

Biology IBiology I

Humans are difficult to study-produce few offspring

-mature slowly with long reproductive cycle

-controlled breeding is unethical

-scientists have studied human genes directly or by looking for patterns in population studies

Human ChromosomesHuman Chromosomes To analyze chromosomes, biologists To analyze chromosomes, biologists

photograph cells in mitosis photograph cells in mitosis (chromosomes are condensed) (chromosomes are condensed)

Biologists then cut out the Biologists then cut out the chromosomes from the photograph chromosomes from the photograph and group them together in pairsand group them together in pairs

KaryotypeKaryotype- picture of chromosomes - picture of chromosomes arranged in pairsarranged in pairs

Human ChromosomesHuman Chromosomes

Human body cells have Human body cells have 46 46 chromosomeschromosomes

2 of the 46 are 2 of the 46 are sex chromosomes sex chromosomes whichwhich determine an individual’s sexdetermine an individual’s sex

Females have two large Females have two large XX chromosomeschromosomes Males have 1 Males have 1 XX and 1 small and 1 small YY 44 of the 46 chromosomes are 44 of the 46 chromosomes are

autosomalautosomal chromosomes or chromosomes or autosomesautosomes

-All human egg cells carry a single X chromosome

-Half of the sperm cells carry an X and half carry a Y

-Thus, half the zygotes will be XX and half XY

XXXX

XY XY

X

Y

X

X

-Males and females are born in a roughly 50:50 ratio because of segregation in meiosis

-Human genes are inherited according to the principles of Gregor Mendel and his work with garden peas

-Biologists study how traits are passed from one generation to the next using a Pedigree chart

Pedigrees-show relationships within a family

-genetic counselors analyze pedigrees to infer genotypes of family members

PedigreesPedigrees

Many traits can’t be Many traits can’t be traced easily because traced easily because they are polygenic they are polygenic and influenced by the and influenced by the environmentenvironment

For those that can, For those that can, pedigrees can pedigrees can predict how a trait predict how a trait and the genes that and the genes that control it are control it are inheritedinherited

Square-male Circle-female

Full color- trait expressed

Half color- carrier of the trait

Roman Numerals- generation

Numbers- individuals

?- unknown genotype

Horizontal line between parents- marriage

Vertical line- children

A circle represents a female.

A square represents a male.

A horizontal line connecting a male and female represents a marriage.

A vertical line and a bracket connect the parents to their children.

A half-shaded circle or square indicates that a person is a carrier of the trait.

A completely shaded circle or square indicates that a person expresses the trait.

A circle or square that is not shaded indicates that a person neither expresses the trait nor is a carrier of the trait.

Figure 14-3 A Pedigree

What do you know about person II-2?What do you know about person II-2? Is the trait for Is the trait for hitchhiker’s thumbhitchhiker’s thumb

dominant or recessive? How do you dominant or recessive? How do you know?know?

Which individuals are carriers?Which individuals are carriers?

Tt Tt

tt ttT_T_

Tt Tt

-1st genes to be identified were those that control blood type

-Blood Types are A, B, AB, and O

-There are also Rh blood groups

-Single gene with two alleles

-Positive or Negative

-Rh is from the Rhesus monkey, the animal in which this factor was discovered

-Many human genes have become known through the study of genetic disorders-Recessive genetic disorders are not expressed in the phenotype of the heterozygote-Heterozygous individuals are carriers-Existence of carriers allows the defective gene to remain in the gene pool, whereas many dominant alleles are reduced in numbers since homozygous individuals often do not survive - Being a carrier usually does not affect health of individual

- Children can’t break down phenylaline found in milk (lack the enzyme)

- Buildup damages nerve cells and causes severe retardation

-May be controlled by diet

-Testing at birth is now required

-Caused by an autosomal recessive allele on chromosome 12

-Fatal genetic disorders among Jewish community from central Europe

-Inability to breakdown a lipid, causing accumulation of a substance in the brain

-Blindness, seizures, and short life

-There is no treatment, but there is a test for the allele, so parents can learn if they are at risk

-Found predominately in Caucasians

-Recessive allele found on chromosome number 7

-Caused by a small genetic change- deletion of 3 bases in the middle of protein sequence

-Excessive secretion of thick mucus which accumulates in the pancreas, lungs and other organs

-The deletion removes 1 amino acid causing the protein to fold incorrectly

Chromosome # 7

CFTR gene

The most common allele that causes cystic fibrosis is missing 3 DNA bases. As a result, the amino acid phenylalanine is missing from the CFTR protein.

Normal CFTR is a chloride ion channel in cell membranes. Abnormal CFTR cannot be transported to the cell membrane.

The cells in the person’s airways are unable to transport chloride ions. As a result, the airways become clogged with a thick mucus.

The Cause of Cystic Fibrosis

-Always expressed

-Individuals may die before they pass the trait

-Less common than recessive traits

-Dwarfism- achondroplasia

-Huntington’s DiseaseHuntington’s Disease

- fatal- deterioration of nervous system

-symptoms begin in early 40’s- because symptoms appear later in life, alleles may be passed to offspring

Huntington’s DiseaseHuntington’s Disease

-both alleles express themselves in the heterozygous

-heterozygous may show milder or fewer symptoms

Examples: Sickle Cells Anemia

-Abnormal hemoglobin causes a sickle shape of red blood cell

-Red blood cells with sickle cell anemia have a bent and twisted shape, they are more rigid and easily get stuck in capillaries-Heterozygous- mix of normal and sickle cells- they are carriers and have some attacks-Homozygous- all red blood cells sickle shaped and they have painful attacks and blood clots-Caused by a change in one base for making hemoglobin-Heterozygous can be beneficial because they are resistant to malaria

caused by

includeincludeinclude

Concept Map

AutosomolDisorders

Recessive alleles

Dominant allelesCodominant

alleles

Albinism Galactosemia Tay-Sachs disease

Huntington’s disease

Sickle cell disease

Cystic fibrosis Phenylketonuria Achondroplasia Hypercholes-

terolemia

-Chromosomes 21 and 22 are the smallest autosomes

-22 has 43 million base pairs & 21 has 32 million base pairsChromosome 22

-As many as 545 different genes

-Disorders

-Form of leukemia

-Neurofibromatasis- tumor causing nervous system disease

-Long stretches of repetitive DNA that does not code for proteins

-Area is unstable and rearrangement occurs

Chromosome 21- 225 genes

- Disorders

-ALS- amyotrophic lateral sclerosis (Lou Gehrig’s disease)

-Many regions with no genes

As we discover what the larger chromosomes contain, we can learn more about how the arrangement of genes on a chromosome affect gene expression and development

As we learned in Chapter 11, some genes are linked-they are located on the same chromosome

This is true for human genes

-Genes located on the sex chromosomes

-Most are found on the X

-The Y chromosome is smaller and has only a few genes

-There are more than 100 sex-linked genetic disorders

-There are 3 genes associated with color vision and they are found on the X chromosome

-Colorblindness is the inability to distinguish between certain colors

-The most common is red-green colorblindness, found in 1 in 100 males

-X-linked recessive allele

-Females must be homozygous recessive to be colorblind (XcXc)

-Males only need 1 allele for the condition (XcY)

Father(normal vision)

ColorblindNormal vision

Mother (carrier)

Daughter(normal vision)

Son(normal vision)

Daughter(carrier)

Son(colorblind)

Male

Female

Colorblindness

Father(normal vision)

ColorblindNormal vision

Mother (carrier)

Daughter(normal vision)

Son(normal vision)

Daughter(carrier)

Son(colorblind)

Male

Female

Colorblindness

-2 genes control blood clotting

-Found in 1 in 10,000 males

- Individuals can bleed to death from minor cut or suffer internal bleeding from bruises

-Females are usually carriers

-It is believed to have begun in the Royal family of Europe in the 19th century

-It can be treated by giving normal clotting protein

-Progressive weakening and loss of muscle tissue

-Almost all cases are male

-Death by age 20

-Genes consists of about 3,000,000 nucleotides (longest known human gene)

-First symptoms appear in childhood when child has difficulty standing up

-It is caused

by a

defective

muscle

protein

-Females have two X chromosomes

-If males only need 1, why not females? Mary Lyon, a British genetists, discovered in female cells, one X chromosome will randomly be switched off

-The turned off chromosome becomes a dense region in the nucleus called a Barr body

Cats-The gene for coat color is found on the X chromosome-One chromosome may the allele for orange spots and another for black spots-Cells in some parts of the body will inactivate one X and in other parts the other X-As a result a female cat may be a mix of orange and black spots

-Mistakes made in meiosis

-Most common mistake

Nondisjunction- failure of homologous chromosomes

to separate

-Occurs when 2 copies fail to separate

-As a result, an individual has three copies of a chromosome

- trisomy “3 bodies”

-Trisomy 21- individual has 3 copies of chromosome 21

-1 in 800 babies

-Mild to severe retardation, an increase in the susceptibility to disease and birth defects

Down syndrome is correlated with the age of the Down syndrome is correlated with the age of the

mother; older mothers have an increased risk of mother; older mothers have an increased risk of giving birth to a child with Down syndromegiving birth to a child with Down syndrome

Turner’s Syndrome

-Female has only 1 X chromosome

-Sterile- unable to reproduce

-Short

-Sex organs do not develop at puberty

Klinefelter’s Syndrome

- Male with XXY

-Extra X interferes with meiosis and usually prevents individuals from reproducing

-Individuals have been found with XXXY and XXXXYThere have been no cases of babies

born with just a Y which indicates that the X chromosome contains genes necessary for survival and development

Human DNA AnalysisHuman DNA Analysis 6 billion base pairs exist in the human 6 billion base pairs exist in the human

genomegenome Can’t read them like a book, there are too Can’t read them like a book, there are too

manymany Genetists “look up” gene sequences to find Genetists “look up” gene sequences to find

disorders and traitsdisorders and traits To test for disorders, genetists look for To test for disorders, genetists look for

changes in the normal sequencechanges in the normal sequence DNA fingerprinting- used to identify peopleDNA fingerprinting- used to identify people

Look at DNA with little or no function, but Look at DNA with little or no function, but varies from person to personvaries from person to person

Human Genome ProjectHuman Genome Project Project to analyze Project to analyze

the human DNA the human DNA sequencesequence

Scientists have Scientists have found there are found there are very few genes very few genes despite all of the despite all of the base pairs that base pairs that existexist

Scientists when Scientists when searching for searching for genes look for genes look for promoters- promoters- binding sites for binding sites for transcriptiontranscription

Promoter Start signal

Gene Stop signal

Normal hemoglobin gene

Bone marrow cell

Chromosomes

Genetically engineered virus

Nucleus

Bone marrow

Gene TherapyGene Therapy

Cure for genetic disordersCure for genetic disordersAbsent or faulty gene replaced by a normal working Absent or faulty gene replaced by a normal working genegene