What’s a “mutagen”?What does a mutation do to DNA?

If a mutation affects a gene, then what might happen to the protein sequence?

Some geneticdisorders are caused by mutations and errors in the DNA code

GENETIC DISORDERS

Point mutation: a single base pair is substituted for another (ex. A C)

TYPES OF MUTATIONS

Insertion/deletion: results in a “frameshift”mutation (how codons are read, ordered, or sequenced)

TYPES OF MUTATIONS

Large scale mutations: duplications/deletions of large chromosome sections; inversions that reverse gene sequences; translocations that exchange parts of nonhomologous chromosomes

TYPES OF MUTATIONS

In autosomal dominant disorders, you only need 1 copy of the allele to have the disease/trait

AUTOSOMAL DOMINANT DISORDERS

A neurodegenerative genetic disorder where nerve cells slowly break down

HUNTINGTON’S DISEASE

Results in uncontrollable muscle movements and mental deterioration

HUNTINGTON’S DISEASE

Caused by a defect on the 4 th chromosome where the triplet CAG repeats more times than it should – the more triplets, the earlier the onset of the disease

HUNTINGTON’S DISEASE

Symptoms normally don’t appear until age 30-50

HUNTINGTON’S DISEASE

If you found out that one of your parents has Huntington’s disease, would you choose to be tested for it yourself? (Yes or No)

BIOETHICS QUESTION OF THE DAY

If you found out that you, yourself, have Huntington’s disease, would you choose to have children? (Yes or No)

BIOETHICS QUESTION OF THE DAY

In autosomal recessive disorders, you need two copies of the allele in order to have the disease/trait

AUTOSOMAL RECESSIVE ALLELES

CYSTIC FIBROSIS

Defective allele on chromosome 7 results in a faulty protein

Causes a thick, heavy mucus to build up and clog the lungs.

Need two recessive alleles - people with one normal chromosome

produce enough of the correct protein

CYSTIC FIBROSIS

CYSTIC FIBROSIS

People with cystic fibrosis

have problems breathing and digesting and are more vulnerable to lung infections

CYSTIC FIBROSIS

Approximately 30,000 children and adults in the U.S. have cystic fibrosis.

About 1 in every 31 Americans are carriers of the defective CF gene, but do not have the disease.

CF is most common in Caucasians, but it can affect all races. (via the Cystic Fibrosis Foundation)

Red blood cells form a bent shape because of misshapen hemoglobin (carries oxygen in the blood)

SICKLE-CELL ANEMIA

SICKLE-CELL ANEMIA

People with sickle-cell suffer from painful episodes, fatigue, shortness of breath, and other health problems(hemoglobin carries oxygen in the blood).

One single base change to the normal allele results in sickled-cells.

SICKLE-CELL ANEMIA

One single base change to the normal allele results in sickled-cells.

SICKLE-CELL ANEMIA

Malaria is a mosquito-transmitted disease caused by a parasite that infects red blood cells,

More common in central parts of Africa, South America, and southern Asia.

SICKLE-CELL AND MALARIA

People who are heterozygous for the trait (who have only one sickle-cell allele) are resistant to malaria but still have enough hemoglobin to function well.

SICKLE-CELL AND MALARIA

A disease where the body cannot break down the amino acid phenylalanine

PHENYLKETONURIA (PKU)

PHENYLKETONURIA (PKU)

A missing enzyme causes phenylalanine to build up in the body; can eventually cause brain damage if the disease is not managed

PHENYLKETONURIA (PKU)

Build of lipids in the central nervous system (CNS)

– usually causes death by age 4

TAY-SACHS DISEASE

More common in specific populations

TAY-SACHS DISEASE

ColorblindnessDecreased ability to see or distinguish

between certain colorsRed-green colorblindness, blue-yellow colorblindness

EXAMPLES OF X-LINKED DISORDERS

Decreased ability to see or distinguish between certain colorsRed-green colorblindness, blue-yellow colorblindness

EXAMPLES OF X-LINKED DISORDERS

EXAMPLES OF X-LINKED DISORDERS

HemophiliaA bleeding disorder that prevents

blood from clotting properly The person bleeds more than

someone without hemophilia

EXAMPLES OF X-LINKED DISORDERS

Duchenne Muscular DystrophyA disorder that involves rapidly

increasing muscle weakness and loss of muscle tissue

Moving on…

Some genetic disorders are caused by chromosomal mutations

GENETIC DISORDERS

A karyotype allows you to see all of the chromosomes in a single cell of an organism

GENETIC DISORDERS

With a karyotype, you can easily observe if there are any extra/missing chromosomes.

GENETIC DISORDERS

How many chromosomes do normal humans have?

46

KARYOTYPES

How many are autosomal chromosomes?

44

KARYOTYPES

How many are sex chromosomes (determine sex of the organism?)

2

KARYOTYPES

Looking at a karyotype, we can very easily observe if the organism has any extra or missing chromosomes that can result in certain genetic disorders.

KARYOTYPES

“not coming apart”The most common error in meiosisOccurs when homologous chromosome

pairs fail to separate during anaphase I or II, resulting in a sex cell with an extra or missing chromosome.

NONDISJUNCTION

NONDISJUNCTION

1. Down Syndrome (Trisomy 21) Three copies of chromosome 21

NONDISJUNCTION DISORDERS

2. Turner’s Syndrome (X) Only one copy of the X chromosome (no

Y)

NONDISJUNCTION DISORDERS

3. Klinefelter’s Syndrome (XXY) Two copies of the X chromosome and a

Y

NONDISJUNCTION DISORDERS

A diagram that shows the inheritance pattern of a trait over many generations is called a pedigree.

PEDIGREES

HOW TO READ A PEDIGREE

Male Female

Pedigree Symbols

Children/ Marriage Siblings

I

II

III

Affected Carrier Person

Looking at a family pedigree, we observe how certain traits have been passed down from parents to offspring and also how certain traits and genetic disorders are expressed.

HOW TO READ A PEDIGREE

How many males vs. females are affected?

Autosomal Dominant = EQUAL

AUTOSOMAL DOMINANT INHERITANCE

Does it skip generations?Autosomal Dominant = NO

AUTOSOMAL DOMINANT INHERITANCE

Who does not express the trait?Autosomal Dominant = Homozygous

recessive individuals

AUTOSOMAL DOMINANT INHERITANCE

How many males vs. females are affected?

Autosomal Recessive = EQUAL

AUTOSOMAL RECESSIVE INHERITANCE

Does it skip generations?Autosomal Recessive = YES

AUTOSOMAL RECESSIVE INHERITANCE

Who does not express the trait?Autosomal Recessive = Either sex, with

at least one dominant allele

AUTOSOMAL RECESSIVE INHERITANCE

How many males vs. females are affected?

Sex-linked Recessive = MORE MALES

X-LINKED RECESSIVE INHERITANCE

Does it skip generations?Sex-linked Recessive = Yes, but

all affected men will inherit trait from mothers

X-LINKED RECESSIVE INHERITANCE

Who does not express the trait?Sex-linked Recessive = Female

carriers

X-LINKED RECESSIVE INHERITANCE

X-LINKED INHERITANCE: A CASE STUDY