Ch. 12 Notes

(1)

(2)

DNA organization

• _{1 human chromosome set= 3billion base pairs!} • _{DNA Packing: double helix} wrapped around

histones (proteins)  tight helical fiber  further coiling: supercoil loop and fold in chromosome

(3)

The Human Genome Project

• _{Complete mapping of all of the nucleotides} (1990-2000)

• _{Genes (regions of DNA that code for proteins)}

must be differentiated from non-coding regions

• _{Functions of all of the polypeptides must be}

determined

• _{Compare human and other species}

(4)

Concept Check 12.1

1. Draw a simple diagram showing the different levels of DNA-packing within a nucleus.

(5)

Accidents affecting chromosomes



may

cause disorders

• _{Meiosis usually distributes chromosomes}

evenly to daughter cells without error

• _{Down Syndrome}

– _“_{trisomy 21}_{”: 3 copies of 21}st_{chromosome pair}

– _{1/700 US births; often results in miscarriage}

– _{below average height, heart defects, shorter life}

span, characteristic facial features

(6)

(7)

• _{Klinefelter’s Syndrome}

– _{XXY male (extra X)}

– _{less facial hair, less muscular}

• _{Turner’s Syndrome}

– _{X_ female (single X)}

– _{Usually sterile, physical}

abnormalities, health problems

• _{Trisomy 13 (Patau Syndrome)}

– _{extra chromosome 13}

– _{occurs in 1 of 10,000 births}

(8)

Non-separation of chromosomes

• _{Abnormal chromosome numbers usually}

caused by nondisjunction: homologous

chromosomes don’t separate during meiosis

• _{occurs in meiosis I or II}

• _{gamete has an extra chromosome}

• _{trisomy 13 more common in older women}

– _{Eggs stuck/paused at stage of meiosis longer}_

(9)

(10)

Damaged Chromosomes

• _{Changes in chromosome structure may cause disorders}

• _Duplication_{: part of chromosome}_repeated

– _{often cause developmental abnormalities}

• _Deletion_{: fragment of chromosome}_lost

– _{Don’t produce proteins coded by those genes}

• _Inversion_:_flip_{a fragment of chromosome}

– _{Less harmful}

• _{Translocation}_{: fragment of one chromosome attaches}

to a non-homologous chromosome

– _{Sometimes non-homologous chromosomes exchange}

(11)

(12)

Jumping Genes

• _{A.k.a “}_transposons_”

• _{Discovered by Barbara McClintock}

• _{Single gene moves to different location}

– _{On same chromosome or to different}

chromosome

• _{Land in other genes and disrupt them}

• _{Ex: cause spotted corn kernels by disrupting}

(13)

Concept Check 12.2

1. What is the relationship between trisomy 21 and Down syndrome? Describe how nondisjunction can result in trisomy 21.

2. List and define four types of damage to chromosome structure that can cause disorders.

3. What is a "jumping gene," or transposon?

(14)

(15)

Human Pedigrees

Human trait inheritance studied by studying family history

Pedigree: family tree with information on the occurrence of a trait in a family

Males: square

Females: circle

Has the trait: Colored in

(16)

Genotypes: determined from trait inheritance patterns

(17)

(18)

Pedigrees are used to analyze

inherited recessive disorders

Most human genetic disorders recessive

– Ex: Albinism, Phenylketonuria, Cystic Fibrosis

Most individuals with disorder born to heterozygous-carrier parents

Carrier: Heterozygous parent with one copy of recessive gene for disorder, but no symptoms

PROBLEM:

(19)

Example Recessive Disorder: Cystic

Fibrosis

Results from inherited

recessive mutated gene

Causes thick mucous buildup in lungs, digestive tract

interferes with breathing, digestion, liver function

Statics of Inheritance:

1/25 people of European ancestry are carriers (4%)

1/625 chance two carriers

having offspring together

1/2500 (0.04% chance) of

(20)

Disorders from Dominant alleles

Example: achondroplasia (form of dwarfism)

1/25,000 (0.004%) people heterozygous (Dd) = cause achondroplasia

Homozygous dominant (DD) = lethal

>99.99% people Homozygous recessive (dd) = normal

(21)

Lethal Dominant disorders (vs.

lethal recessive)

Lethal recessive alleles more common because:

– _{Usually do not affect a carrier}

– _{More likely to be passed on to offspring from two carriers}

Lethal dominant alleles less common because:

(22)

Lethal Dominant disorders

Some lethal alleles don’t show till adulthood

Example: Huntington’s Disease:

– _{Rapid nervous system degeneration leads to death}

– _{Disease doesn’t show up till middle age (maybe already}

passed to offspring)

– _{Mutant gene now pinpointed to chromosome 4 (can be}

(23)

Sex linked disorders

Mostly caused by recessive alleles on X chromosome

Mostly found in males

– _{Males only need one allele (from carrier/diseased}

mother) to inherit the trait

– _{Females need two alleles (from}_both_parents).

(24)

(25)

(26)

Predicting and Treating genetic

disorders

Genetic counselor:

*Analyzes family history (pedigree) for inheritance patterns of disorders

*Help parents assess risk of passing on disorders

Example: helps a pair of carrier parents prepare for risks of having a child with Cystic Fibrosis

(27)

Predicting and Treating genetic

disorders

Tests on baby pre-birth also help inform parents

Ex: Karyotype test for Down Syndrome, Trisomy-13

• _{Prepare parents for treatment options}

Ex: Blood test for Phenylketoneuria (PKU)

• _{Treatment: regulate diet to avoid complications from}

(28)

HW

Concept Check 12.3

1. What information is collected to create a pedigree for a particular trait?

2. Give examples of a recessive disorder, a

dominant disorder, and a sex-linked recessive disorder, and describe how each is inherited.

(29)

Cancer results from multiple gene

mutations

1st_mutation:

Oncogene (a cancer causing gene)

– _{Often a}

growth-factor gene mutated to become

over-active

– _{Stimulates cell to}

(30)

Cancer results from multiple gene

mutations

2nd_{mutation: mutated}

tumor-suppressor gene

– _{Normally stops cell}

growth when new cells aren’t needed or DNA is damaged

– _{Mutated gene does not} stop abnormal cell

(31)

Cancer results from multiple gene

mutations

Additional mutations: tumor becomes

malignant :

Cancer cells can spread

_{cause more tumors}

(32)

(33)

Inherited Cancer

Many cancer mutations occur in specific organ cells of individual (Example: skin cancer)

– _Usually_NOT_{able to be passed on}

Some mutations occur in a gamete-producing cell:

– _Mutation_may_{be passed on via gametes}

– _{Inherited gene increases risk of cancer in offspring}

Example: mutant BRCA1 gene (tumor-suppressor gene)

(34)

Concept Check 12.4

1. Compare and contrast the two classes of genes involved in regulating the cell cycle.

2. Describe how a woman inheriting a mutated

BRCA1 gene is at a higher risk for breast cancer.