The Human GenomeChapter 12-1 & 12-2

THINK ABOUT IT

What does a can of Diet Coke and this songhave to do with human

genetics?(Answers to come in this slide show!)

HUMAN GENETICSDominant and

Recessive

Homozygous/Heterozygous

work for human genes too!

________ are made by joining___________ subunits togetheramino acid

Proteins

REMEMBER YOUR MOLECULES!

REMEMBER YOUR MOLECULES

__________ is carried in the ________ of A, T, G, C’s on a_____ moleculeDNA

Genetic code

sequence

The sequence of A’s, T’s, G’s & C’stells the _______ of ________ in the

________

ORDER amino acidsprotein

Changes in the gene code _______________ that is made

A change in the genetic code =________________

MUTATION

change the protein

KINDS OF MUTATIONS________ CELLS = ___________ CELLS

Somatic cell mutations can: ______________________

______________________

_____________

BODY

Cause cancer

Make cell not able to function

Kill cell

BUT _________ passed on to offspring

WON’T BE

SOMATIC

Kinds of Mutations

___________ = _________cells(sperm & eggs)

GAMETES

Germ cell mutations ________ passed on to offspring

CAN BE

http://anthro.palomar.edu/biobasis/images/meiosis.gif

GERM

Mistakes in Meiosis

• Examples:

– Down’s Syndrome (Trisomy-21)

– Klinefelter’s Syndrome

– Turner’s Syndrome

• Chromosomes fail to separate properly during meiosis, i.e., nondisjunction

• ANEUPLOIDY -- an abnormal number of chromosomes

____________- Most mutations have little or no effect on gene ____________.

_____________ in code can absorb many mutations without changing theamino acid sequence.

UUC and UUU bothcode for same amino acid

MUTATIONS can be:

NEUTRALfunction

REDUNDANCY

____________ - Mutations that produce ______________ are usually harmful.

Harmful mutations are associated with many________________ and can cause____________

MUTATIONS can be:

HARMFULdefective proteins

genetic disorderscancer

____________ - Some mutationschange proteins that are so vital to life that they cause death, usually before birth.

50% of pregnancies that abort spontaneously have genetic abnormalities

MUTATIONS can be:

LETHAL

Mutations can help an organism _________________

Provide a way for species to changeover time

____________- Mutations are also a source of ______________ in thepopulation

MUTATIONS can be:

BENEFICIALgenetic variation

survive and reproduce

Mutations can happen:• when cells make_________ in copying DNA• when cells are exposed to environmental ___________ like __________- X-rays, tanning booths

__________ - cigarette smoke, pollutants__________ - HPV

_______________ are changes in the genetic material.MUTATIONS

mistakes

REMEMBER!

carcinogensradiationchemicalsviruses

Mutations that produce changes in a single gene = _________________

Mutations that produce changes in whole chromosomes = _____________________

KINDS OF MUTATIONS

GENE MUTATIONS

CHROMOSOMAL MUTATIONS

Images from: http://www.bbc.co.uk/scotland/education/bitesize/higher/img/biology/genetics_adaptation/mutations/02gene_mutation.gif

MANY HUMAN GENES HAVE BECOME

KNOWN THROUGH THE STUDY OF GENETIC DISORDERS

Many genetic ___________ result fromchanges in the DNA code so

_________________ proteins are produced.

DISORDERS

NON-FUNCTIONING

http://patentdocs.typepad.com/photos/uncategorized/2007/05/28/dna1.gif

A mutation that causes a protein to beNON-FUNCTIONAL would appear_______________ to the normal working allele.

Examples of __________________________ GENETIC DISORDERS:

____________________

____________________

____________________

RECESSIVE

PHENYLKETONURIA (PKU)

TAY-SACHS DISEASE

CYSTIC FIBROSIS

AUTOSOMAL RECESSIVE

Phenylketonuria (PKU)

CAUSE: Mutation in gene for an ___________ that __________ an ___________ called phenylalanine

Build up causes ________________________MENTAL RETARDATION

ENZYME

http://biology.clc.uc.edu/courses/bio104/protein.htm

breaks down amino acid

X

X

Phenylketonuria (PKU)

____ babies are ________for PKU before they leave the hospital.

Treatment: Need a diet _____________________ to extend life and ______________ mental retardation

If phenylalanine is an _____________, what type of foods should PKU patients avoid? __________________

amino acid

PROTEINS !

LOW in phenylalaninePREVENT

ALL tested

http://labspace.open.ac.uk/file.php/2588/SK195_6_002i.jpg

THINK ABOUT IT

What does a can of Diet Coke have to dowith human genetics?

LOOK AT THE WARNING LABEL !

______________ is made with phenylalanineNUTRASWEET

Common Pedigree SymbolsMale

FemaleMarriage

Affected Female

Female Carrier of Sex-linked Recessive

Sex Unknown

Consanguineous Marriage

No Known Pregnancy

Unmarried

DeadDivorce and Remarried

Female Carrier (Heterozygous)

Common Pedigree Symbols

Pregnancy in Progress

3 Three Males

5Five Individuals (both sexes)

Dizygotic (nonidentical, fraternal) twins

Monozygotic (identical) twins

Spontaneous Abortion

Proband, propositus, or index case

Adopted Child

Bad DivorceFamous Kid

Triplets!

Happy new wife!

TAY-SACHS DISEASE___________________

CAUSE: Mutation in gene for an ___________ that breaks down a kind of _________in the developing _________

Build up of lipids in brain cells leads to:mental retardation, blindness, and DEATH in early childhood

Found more frequently in people with _______ _____________ ______________, ancestry

BRAIN

ENZYME

Jewish

Image from: http://www.djsfoundation.org/images/Steeler%20pics%20Dylan.jpg

AUTOSOMAL RECESSIVE

Mediterranean Middle Eastern

LIPID

Autosomal Recessive• Disease manifests itself if offspring inherits one

recessive gene from each parent.• If parents are carriers, 25% of offspring will

have disease.

Tay-Sachs Disease• 1 in 600 Jews of European descent born with it• Lipids deposited in nervous system, causing brain to be damaged -- blindness, loss of

movement, mental deterioration.• No break down of cellular wastes in lysosome due to absence of hexosaminidase A –

mutation causes nerve death

• Symptoms appear around 6 months of age and victims die due to paralysis and/or convulsions before the age of five.

Tay-Sachs Disease

What are the genotypes of all individuals in this family?

Tt Tt

tt

TtTt

TT or Tttt Tt or TTTt or TT

TT or Tt

http://www.biochem.arizona.edu/classes/bioc460/spring/rlm/RLM36.1.html

A __________ person who carries a _________ allele for a genetic disorder, but ______________ the disorder themselves is called a_____________CARRIER

heterozygous

doesn’t show

recessive

Polygenic Inheritance

• Most human characteristics are polygenic, meaning they are influenced by several genes, e.g. skin color influenced by 3-6 genes; also, eye color, height, hair color

• Complex characters are those that are influenced strongly by both the environment and genes, e.g., diabetes, heart disease, stroke, skin color, height

More patterns of inheritance…..

• Multiple alleles - genes with three or more alleles, e.g., ABO blood groups

• Incomplete dominance – condition that results in a display of a trait that is intermediate between the two parents

• X-linked traits – determined by x-linked genes, e.g., color blindness

• Sex-influenced traits – usually autosomal, e.g. baldness is influenced by testosterone

• Single-allele traits – more than 200 human traits are governed by single dominant alleles, e.g., Huntington’s disease

Single Gene Inheritance

• Autosomal dominant traits– Huntington’s Disease on chromosome #4– Marfan Syndrome on chromosome #15– Breast Cancer on chromosomes #17

Pedigree Analysis

• Autosomal recessive traits– Tay-Sachs Disease on chromosome #15

– Cystic Fibrosis on chromosome #7

– Sickle Cell Anemia on chromosome #11

• X-Linked Disease (Sex-Linked)– Hemophilia --Duchenne’s muscular dystrophy

– Color Blindness

Multiple Alleles• Blood type, using I gene.• Human blood types include:

Phenotype Genotype– A IAIA or IAi– B IBIB or IBi– AB IAIB (Universal Recipient)– O ii (Universal Donor)

If a child has type O blood and its mother has type A, could a type B man be the father? Why couldn’t a blood test be used to prove he is the father?

CYSTIC FIBROSIS CAUSE:

Loss of 3 DNA bases in a gene for the _____________ that transports _________ so salt balance is upset

Causes a build up of _________________ in lungs and digestive organs

.

thick mucous

protein

Image from: BIOLOGY by Miller and Levine; Prentice Hall Publishing ©2006

Cl- ions

Cystic Fibrosis• Found in Caucasians.

– Most common lethal genetic disorder among white Americans.

– Autosomal recessive on chromosome 7

• Thick mucus produced in lungs, intestines, and pancreas.

• 1/20 of Caucasian population are carriers.– One in 2,000 children born to white Americans inherits

the disorder.– CF kills ~500 children and young adults each year.

A mutation that codes for a new proteinwhose action masks the normal alleleappears as a ______________ mutation.

Examples of _________________________ GENETIC DISORDERS:

____________________

____________________

DOMINANT

Huntington’s disease

Achondroplasia

AUTOSOMAL DOMINANT

HUNTINGTON’S DISEASE______________________

CAUSE: Extra 40-100 ______________ at end of gene on chromosome 4

The _____________ . . . the more __________ the symptoms.

severe

CAG repeats

http://www.healthsystem.virginia.edu/internet/huntdisease/images/cag.gif

more repeats

AUTOSOMAL DOMINANT

HUNTINGTON’S DISEASE

Causes progressive _____ of ________________ and ___________function

loss

muscle control

mental

1 in 10,000 people in U.S. have Huntington’s disease

http://www.scielo.br/img/revistas/bjmbr/v39n8/html/6233i01.htm

Huntington’s brain

Normal brain

A person with Huntington’s disease has a _____ chance of passing the disorder on totheir offspring.

Problem:Symptoms of disorder usually don’t show until ____________ . . .

so you don’t know you have it until ________ you have had children.

50%

MIDDLE AGE

AFTER

Huntington’s Disease

• Begins to show up by age 45-55, within 10-20 years, death is eminent.

• Progressive degeneration of nervous system; irregular body movements and slurred speech.

• If one parent has HD, offspring have 50% chance of inheriting disease.

• Autosomal dominant on chromosome 4; 1 in 10,000 births

Huntington’s Disease

What are the genotypes of the parents?

Hh hh

THINK ABOUT IT

What does the songhave to do with human genetics?

“This Land is My Land” was written by a musician named Woody Guthrie before he began to show the symptoms of Huntington’s disease.

Click to hearWoody’s song

Woody Guthrie had a son named Arlo that was a popular musician during the 70’s

Before 1993 there was no test for Huntington’s.

If one of your parents showed symptoms, you had to wait to see if it had been passed on to you.

Click to hear one of Arlo’s songs

Arlo Guthrie is still performing today.

He never developed symptoms for Huntington’s disease.

http://www.jimdirden.com/woodyfest2004/artists/index_3.htm

If there is no cure, would YOU want to be tested and find out if you have the gene?

http://webs.wichita.edu/depttools/depttoolsmemberfiles/accomp/question_mark%20(WinCE).jpg

ACHONDROPLASIA(One kind of Dwarfism)

CAUSE: ___________________________ gene

200,000 “little people” worldwide

One of oldest known disorders – seen in Egyptian art

AUTOSOMAL DOMINANT

1 in 20,000 births

ACHONDROPLASIA(One kind of Dwarfism)

Normal size head and torso; short arms and legs

Problem with way cartilage changes to bone as bones grow

DISORDERS CAUSED BY ____________________

____________________SICKLE CELL DISEASE

CAUSE: T changed to A in gene for

__________________ (protein in red blood cells that carries oxygen in blood)

HEMOGLOBIN

AUTOSOMAL CODOMINANT ALLELES

SICKLE CELL DISEASE

SYMPTOMS:_____________ become sickle shaped in persons with ______ sickle cell ________

RED BLOOD CELLS

TWOALLELES

SICKLE CELL DISEASE

Circulatory problemsCells stick in capillariesLoss of blood cells (anemia)Organ damage (brain, heart, spleen)Can lead to DEATH

SICKLE CELL DISEASEMore common in _________________ 1 in 500 = have sickle cell disease 1 in 10 = carriers for allele

Also affects persons of _______________ and _________________ descent

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

AFRICAN AMERICANS

MEDITERRANEANMIDDLE EASTERN

SICKLE CELL DISEASEMany can trace their ancestry to

westcentral Africa where ___________,a serious parasitic disease thatinfects red blood cells is common.

Images from: http://en.wikipedia.org/wiki/Malaria

MALARIA

Watch a video about sickle cell and malaria

A person who is __________________ for the ____________allele (ss) will have _______________

A person who is _________________ for normal hemoglobin alleles will have normal blood cells, but can become infected with __________ (SS)

A _________________ person (Ss)(with one normal/one sickle cell allele) isgenerally healthy and has the benefit ofbeing _________ to malaria

HOMOZYGOUSsickle cell

sickle disease

HOMOZYGOUS

malaria

HETEROZYGOUS

resistant

A __________ is a picture of an organism’s chromosomes

KARYOTYPE

Chromosomes that determine the sex of an organism = _________________

All other chromosomes = _________________

Sex chromosomes

autosomes

Humans have two sex chromosomes

and _____ autosomes

X y44

http://www.angelbabygifts.com/

SEX DETERMINATIONXX =

Xy =

female

male

Who decides?

Mom can give X

Dad can give X or y

SO ____ determines sex of the baby.

If dad gives X with mom’s X = girlIf dad give y with mom’s X = boy

X X

X

y

X X X X

X y X y

Dad

SEX CHROMOSOMES CAN CARRY OTHER GENES TOO= ___________________SEX LINKED TRAITS

These traits show up in different _______________ in males and females because they move with the sex chromosomes

percentages

Y-LINKED GENES: Genes ______________ chromosome

EXAMPLE:Hairy pinna

_________genes _____ show up _______Y linked in males

carried on Y

ONLY

____________ GENES: are carried on the X chromosome

X-linked recessive disorders show up _____________in ______ than femalesbecause males only have______ X chromosome.

MALES

X-LINKED

ONE

MORE frequently

Males ONLY HAVE ONE X

They eitherhave the disorder

DEFECTIVE NORMAL

They are normal

Or

FEMALES HAVE TWO X CHROMOSOMES

Females have one normalgene that works.

NORMAL DEFECTIVEDEFECTIVE

Females __________defective recessivealleles to show the disorder

need 2

The X chromosome in males . . . flies WITHOUT a copilot!

. . . there’s NO BACK UP X to help them!

Examples of ________________________ DISORDERS:

____________________

____________________

____________________

HEMOPHILIA

COLORBLINDNESS

DUCHENNE MUSCULAR DYSTROPHY

X-LINKED RECESSIVE

HEMOPHILIA CAUSE:

Mutation in genes for __________________ carried ______ chromosome

Blood clotting proteins are missing so person with this disorder can’t stop bleeding when injured; can ________________ from minor cuts or suffer internal bleedingfrom bruises or bumps.

bleed to death

Blood clotting proteinson X

Hemophilia -- “Bleeder’s Disease”• Deficient blood coagulation due to absence of coagulation factor 8 that helps cause

blood to clot.

• 50% of daughters will also be carriers.

XHXh XHY

• 1 in 7,000 born with it• X-linked recessive on chromosome X

HEMOPHILIA Treatment:

Need ____________ of normal clotting proteins to stop bleeding

_____________ in ______ because it is X-linked, but females with ______ recessive hemophilia alleles will also show the trait.

1 in 10,000 males has hemophilia

injections

malesTWO

More common

COLORBLINDNESS CAUSE:

Mutation in one of three genes for _______________ carried on X chromosome

Persons with this disorder have trouble distinguishing colors.

_________________ colorblindness is most common

Seen in 1 in 10 males 1 in 100 females

Red-green

Color vision

http://gizmodo.com/gadgets/peripherals/samsung-develops-lcd-for-colorblind-036306.php

Red-Green Color Blindness

Duchenne Muscular DystrophyCAUSE: deletion in genethat codes for a_______________

Results in ____________________and loss of

___________________

http://www.cadenhead.org/workbench/gems/jerry-lewis-telethon.jpghttp://www.tokyo-med.ac.jp/genet/chm/dei.gif

muscle protein

progressive weakeningskeletal muscle

Duchenne Muscular Dystrophy (DMD)

SYMPTOMS: 1 in 3000 male births Appears before age 5 Progressive muscle weakening Most in wheelchair by age 13 Eventually lethal

What’s the pattern: ________ traits show up _______ in _______

__________________ traits: ______________________ than females. ________________ can be ________.

_______________________ traits:BOTH ______ & _________ can be ________

Y-linked ONLY males

X-linked recessivemore common in males

AUTOSOMAL RECESSIVE

ONLY FEMALES carriers

MALES FEMALES carriers

________________ Abnormalities

• 1 infant in 200 newborns has a chromosomal abnormality • 28% of first trimester miscarriages have a chromosomal abnormality

• Abnormalities in larger chromosomes don’t usually survive

CHROMOSOMAL

____________________________:Change in the ______________ or ____________ of chromosomes

CHROMOSOMAL MUTATIONS

structurenumber

Homologous chromosomes ________________ during MEIOSIS

= _________________________

One cell gets 2 copies of the chromosome the other cell gets none.

NONDISJUNCTION

fail to separate

Nondisjunction

NondisjunctionSince it happens to a

sperm or egg, the new

baby can end up

with _____________ of a

chromosome

= __________________

OR

only ___________ of a

chromosome

= ___________________

TRISOMY

MONOSOMY

3 copies

one copy

Human Abnormalities caused by Non-Disjunction______________________________________________________

Down syndrome

Klinefelter syndrome

Turner syndrome

Down syndrome (= ____________)TRISOMY 21

Down syndrome (Trisomy 21)

• 1 in 800 births

• Similar facial features

• Slanted eyes

• Protruding tongue

Down syndrome (Trisomy 21)

Simian line on palm

Down syndrome (Trisomy 21)• Most common chromosomal

abnormality

• 50% have heart defects that need surgery to repair

• Mild to severe mental retardation

• Increases susceptibility to many diseases

• Risk of having a child with Down syndrome increases with age of mom

Down syndrome (Trisomy 21)• Risk of having a child

with Down syndrome related to age of mom

• More common in women UNDER 16 or OVER 35

Cells that make eggs start meiosis in embryoStop in PROPHASE I (synapsis)One egg restarts & finishs division each monthSo an egg released at age 40 has been in synapsis for 40 years . . . chromosomes more likely to “stick”

Turner syndrome

Turner syndrome ____

• 1 in 5000 births• Females have only one X chromosome• Small size• Slightly decreased intelligence• 35% have heart abnormalities• Hearing loss common• Broad chest• Reproductive organs don’t develop at puberty• Can’t have children

http://medgen.genetics.utah.edu/photographs/diseases/high/611.gif

XO

Klinefelter syndrome XXy

Klinefelter syndrome

• 1 in 1000 births

• Males have extra X chromosomes

(Can be XXy, XXXy, or XXXXy)

• Average to slight decrease in intelligence

• Small testes/can’t have children

• Usually not discovered until puberty when don’t mature like peers

If having extra chromosomes causes genetic problems, how

come having two X chromosomes in females and

one X in males is not a problem?

X-chromosome Inactivation

In female cells ______ chromosome is randomly ________________

It condenses and forms a dense region in the nucleus called a

_____________BARR BODY

http://fig.cox.miami.edu/~cmallery/150/gene/barr.htm

ONE XSWITCHED OFF

In some female cells the X with the allele for orange spots is switched off and in some cells the X with the allele for black spots is switched off, so cat has different colored spots.

CAT COLORIn cats, a gene that

controls the _____________

is carried on the

____________________X chromosome

http://www.islandstrolling.com/mainland/peloponnes/photo/mystra_cat_white_orange_black.jpg

SPOT COLOR

See a video

_________ cats have only one X chromosome, so they can only have ____________ of spots!

CAT COLOR

Male

one color

http://ascensionparish.net/forum/messages/14/2493.jpg

THINK ABOUT IT?How many colors of spots could a male cat withKlinefelter syndrome have?

Detecting Genetic Disease

• Genetic Screening – examination of a person’s genetic makeup involving karyotypes, blood tests for certain proteins, or direct tests of DNA– 200 genetic disorders can be detected in the fetus– Amniocentesis – removal of amniotic fluid from the sac that

surrounds the fetus between the 14th and 16th week of pregnancy– Chorionic villi sampling – sample of cells derived between the

8th and 10th week from the zygote - cells grow between the mother’s uterus and the placenta; cells chromosomes, and proteins analyzed

Detecting Genetic Disease

– Chorionic villi sampling – CVS can help identify chromosomal problems such as Down syndrome or other genetic diseases such as cystic fibrosis, Tay-Sachs disease and sickle cell anemia. CVS is considered to be 98% accurate in the diagnosis of chromosomal defects, such as Down syndrome.