PowerLecture:PowerLecture:Chapter 12Chapter 12

Chromosomes and Human Chromosomes and Human InheritanceInheritance

Genes Genes

Units of information about heritable traitsUnits of information about heritable traits

In eukaryotes, distributed among In eukaryotes, distributed among chromosomeschromosomes

Each has a particular locus Each has a particular locus

Location on a chromosomeLocation on a chromosome

Homologous ChromosomesHomologous Chromosomes

Homologous autosomes are identical in Homologous autosomes are identical in length, size, shape, and gene sequencelength, size, shape, and gene sequence

Sex chromosomes are nonidentical but still Sex chromosomes are nonidentical but still homologoushomologous

Homologous chromosomes interact, then Homologous chromosomes interact, then segregate from one another during meiosissegregate from one another during meiosis

AllelesAlleles

Different molecular forms of a geneDifferent molecular forms of a gene

Arise through mutationArise through mutation

Diploid cell has a pair of alleles at each locusDiploid cell has a pair of alleles at each locus

Alleles on homologous chromosomes may be Alleles on homologous chromosomes may be

same or differentsame or different

Sex ChromosomesSex Chromosomes

Discovered in late 1800sDiscovered in late 1800s

Mammals, fruit fliesMammals, fruit flies

XX is female, XY is maleXX is female, XY is male

In other groups XX is male, XY femaleIn other groups XX is male, XY female

Human X and Y chromosomes function as Human X and Y chromosomes function as

homologues during meiosishomologues during meiosis

Karyotype Preparation - Karyotype Preparation - Stopping the Cycle Stopping the Cycle

Cultured cells are arrested at metaphase by Cultured cells are arrested at metaphase by adding colchicineadding colchicine

This is when cells are most condensed and This is when cells are most condensed and easiest to identifyeasiest to identify

Karyotype PreparationKaryotype Preparation

Arrested cells are broken openArrested cells are broken open

Metaphase chromosomes are fixed and Metaphase chromosomes are fixed and stainedstained

Chromosomes are photographed Chromosomes are photographed through microscopethrough microscope

Photograph of chromosomes is cut up Photograph of chromosomes is cut up and arranged to form karyotype diagramand arranged to form karyotype diagram

Fig. 12-4, p.189

Karyotype Preparation

Autosomal Autosomal Dominant InheritanceDominant Inheritance

Trait typically Trait typically appears in every appears in every generationgeneration

Fig. 12-10a, p. 190

AchondroplasiaAchondroplasia

Autosomal dominant Autosomal dominant alleleallele

In homozygous form In homozygous form usually leads to usually leads to stillbirthstillbirth

Heterozygotes Heterozygotes display a type of display a type of dwarfismdwarfism Have short arms and legs relative to

other body parts

Huntington Huntington DisorderDisorder

Autosomal dominant Autosomal dominant alleleallele

Causes involuntary Causes involuntary movements, nervous movements, nervous system deterioration, system deterioration, deathdeath

Symptoms don’t usually Symptoms don’t usually show up until person is show up until person is past age 30past age 30

People often pass allele People often pass allele on before they know on before they know they have itthey have it

Autosomal Recessive Autosomal Recessive Inheritance PatternsInheritance Patterns

If parents are both If parents are both heterozygous, child heterozygous, child will have a 25% will have a 25% chance of being chance of being affected affected

Fig. 12-10b, p. 191

GalactosemiaGalactosemia

Caused by autosomal recessive alleleCaused by autosomal recessive allele

Gene specifies a mutant enzyme in the pathway Gene specifies a mutant enzyme in the pathway that breaks down lactosethat breaks down lactose

galactose-1-phosphate

enzyme 2

lactose galactose

enzyme 1

+glucose

galactose-1-phosphate

enzyme 3

intermediatein glycolysis

Hutchinson-Gilford ProgeriaHutchinson-Gilford Progeria

Mutation causes Mutation causes

accelerated agingaccelerated aging

No evidence of it running No evidence of it running

in familiesin families

Appears to be dominantAppears to be dominant

Seems to arise as Seems to arise as

spontaneous mutationspontaneous mutation

Usually causes death in Usually causes death in

early teens early teens

x

x

eggs sperm

diploidgerm cellsin female

diploidgerm cellsin male

meiosis, gameteformation in bothfemale and male:

sex chromosomecombinations

possible in newindividual

Fertilization:

XX XX

X

X

Y

X

XX

X

X XY XY

Fig. 12-8a, p.192

Sex Determination

The Y ChromosomeThe Y Chromosome

• Fewer than two dozen genes

identified

• One is the master gene for

male sex determination

– SRY gene (sex-determining

region of Y)

• SRY present, testes form

• SRY absent, ovaries form

• NPR

The X ChromosomeThe X Chromosome

• Carries more than 2,300 genes

• Most genes deal with nonsexual traits

• Genes on X chromosome can be expressed in both males and females

EmbryologistEmbryologist

DrosophilaDrosophila, fruit fly’s , fruit fly’s X chromosome has X chromosome has the gene for eye color the gene for eye color and another gene for and another gene for body color (p193)body color (p193)

D. melanogasterD. melanogaster

Reciprocal crossesReciprocal crosses

Thomas MorganThomas Morgan

Fig. 12-9, p.193

X-Linked Recessive InheritanceX-Linked Recessive Inheritance

Males show disorder Males show disorder more than femalesmore than females

Son cannot inherit Son cannot inherit disorder from his disorder from his fatherfather

Fig. 12-10, p.194

Examples of X-Linked TraitsExamples of X-Linked Traits

Color blindnessColor blindness

Inability to distinguish among some of all colorsInability to distinguish among some of all colors

HemophiliaHemophilia

Blood-clotting disorderBlood-clotting disorder

1/7,000 males has allele for hemophilia A1/7,000 males has allele for hemophilia A

Was common in European royal familiesWas common in European royal families

Fig. 12-12, p.195

Color Blindness

Fig. 12-12, p.195

Color Blindness

Fig. 12-11, p.194

Hemophilia

Duchenne Muscular DystrophyDuchenne Muscular Dystrophy

Rapid degeneration of muscles Starts early, 3-7 yo.1 in 3500 boysEncodes dystropin that supports fused together cells in muscle fibers

Fragile X SyndromeFragile X Syndrome

An X-linked recessive An X-linked recessive

disorderdisorder

Causes mental Causes mental

retardationretardation

Mutant allele for gene Mutant allele for gene

that specifies a protein that specifies a protein

required for brain required for brain

developmentdevelopment

Allele has repeated Allele has repeated

segments of DNAsegments of DNA

DuplicationDuplication

Gene sequence that Gene sequence that

is repeated several to is repeated several to

hundreds of times hundreds of times

Duplications occur in Duplications occur in

normal chromosomesnormal chromosomes

May have adaptive May have adaptive

advantageadvantage

Useful mutations may Useful mutations may

occur in copyoccur in copy

DuplicationDuplicationKaryotype of duplicated chromosomes of the Karyotype of duplicated chromosomes of the gibbon.gibbon.

Fig. 12-14, p.197

DeletionDeletionLoss of some segment of a chromosomeLoss of some segment of a chromosome

Most are lethal or cause serious disorderMost are lethal or cause serious disorder

Common in cancerous cellsCommon in cancerous cells

http://nitro.biosci.arizona.edu/courses/EEB320-2007/Lecture40/lecture40.html

Cri du ChatCri du Chat

Fig. 12-13, p.196

InversionInversionA linear stretch of DNA is reversed A linear stretch of DNA is reversed

within the chromosomewithin the chromosome

Paracentric inversion of short arm

Paracentric inverstion of long arm

Paracentric inversion

http://www.tokyo-med.ac.jp/genet/cai-e.htm

TranslocationTranslocation

A piece of one chromosome becomes attached A piece of one chromosome becomes attached to another nonhomologous chromosometo another nonhomologous chromosome

Most are reciprocalMost are reciprocal

Philadelphia chromosome arose from a Philadelphia chromosome arose from a reciprocal translocation between chromosomes reciprocal translocation between chromosomes 9 and 229 and 22 Reciprocal

translocation

Chromosome StructureChromosome Structure

Alterations to chromosome structure are Alterations to chromosome structure are usually badusually bad

Duplications are adaptive: one gene functions Duplications are adaptive: one gene functions normally - the other is free to mutatenormally - the other is free to mutate

Chromosome structure evolvesChromosome structure evolves

Chromosome StructureChromosome Structure

Human body cells have 23 pairs of Human body cells have 23 pairs of chromosomeschromosomes

Chimpanzees, gorilla, or orangutan body cells Chimpanzees, gorilla, or orangutan body cells have twenty-four pairs of chromosomeshave twenty-four pairs of chromosomes

During human evolution, two chromosomes in During human evolution, two chromosomes in an early ancestor fused to form chromosome 2 an early ancestor fused to form chromosome 2 (p197)(p197)

Fig. 12-15, p.197

chimpanzeehuman gorilla orangutan

Chromosome Chromosome StructureStructure

AneuploidyAneuploidy

Individuals have one Individuals have one extra or less extra or less chromosome chromosome

(2(2nn + 1 or 2 + 1 or 2nn - 1) - 1)

Major cause of human Major cause of human reproductive failurereproductive failure

Most human Most human miscarriages are miscarriages are aneuploids aneuploids

PolyploidyPolyploidyIndividuals have three Individuals have three or more of each type of or more of each type of chromosome (3chromosome (3nn, 4, 4nn))

Common in flowering Common in flowering plantsplants

Lethal for humansLethal for humans

99% die before birth99% die before birth

Newborns die soon after Newborns die soon after birthbirth

Easter Lily (4n), where n=12.

n + 1

n + 1

n - 1

n - 1

chromosome alignments at metaphase I

NONDISJUNCTION AT ANAPHASE I

alignments at metaphase II

anaphase II CHROMOSOMENUMBER INGAMETES

Fig. 12-16b, p.198

Nondisjunction

Down SyndromeDown SyndromeTrisomy of chromosome Trisomy of chromosome 2121

Mental impairment and a Mental impairment and a variety of additional variety of additional defectsdefects

Can be detected before Can be detected before birthbirth

Risk of Down syndrome Risk of Down syndrome increases dramatically in increases dramatically in mothers over age 35mothers over age 35

Turner SyndromeTurner Syndrome

Inheritance of only one X Inheritance of only one X (XO)(XO)

98% spontaneously 98% spontaneously abortedaborted

Survivors are short, Survivors are short, infertile femalesinfertile females

No functional ovariesNo functional ovaries

Secondary sexual traits Secondary sexual traits reducedreduced

May be treated with May be treated with hormones, surgeryhormones, surgery

Klinefelter SyndromeKlinefelter Syndrome

XXY conditionXXY conditionResults mainly from Results mainly from nondisjunction in nondisjunction in mother (67%)mother (67%)Phenotype is tall Phenotype is tall malesmales

Sterile or nearly soSterile or nearly soFeminized traits Feminized traits (sparse facial hair, (sparse facial hair, somewhat enlarged somewhat enlarged breasts)breasts)Treated with Treated with testosterone injectionstestosterone injections

XYY ConditionXYY Condition

Taller than average Taller than average malesmales

Most otherwise Most otherwise phenotypically normalphenotypically normal

Some mentally Some mentally impairedimpaired

Once thought to be Once thought to be predisposed to predisposed to criminal behavior, but criminal behavior, but studies now discreditstudies now discredit

Human Genetic AnalysisHuman Genetic Analysis

Unlike lab animals, weUnlike lab animals, weLive under variable conditionsLive under variable conditions

Live long, select our own matesLive long, select our own mates

Reproduce when we want toReproduce when we want to

Small familiesSmall families

Gather information from several generations Gather information from several generations and create pedigreesand create pedigrees

Pedigree Pedigree Symbols Symbols

male

female

marriage/mating

Individual showing trait being studied

sex not specified

generationI, II, III, IV...

offspring in order of birth, from left to right

Fig. 12-19a, p.200

Fig. 12-19b,p.200

http://www.eatonhand.com/hw/hw024.htm

Abnormality vs. DisorderAbnormality vs. Disorder

A rare, uncommon A rare, uncommon

version of a traitversion of a trait

PolydactylyPolydactyly

Unusual number of toes Unusual number of toes

or fingersor fingers

Does not cause any Does not cause any

health problemshealth problems

View of trait as View of trait as

disfiguring is subjectivedisfiguring is subjective

Inherited conditions that Inherited conditions that

cause mild to severe cause mild to severe

medical problemsmedical problems

Why don’t they Why don’t they

disappear?disappear?

Mutation introduces Mutation introduces

new rare allelesnew rare alleles

In heterozygotes, In heterozygotes,

harmful allele is harmful allele is

masked, so it can still masked, so it can still

be passed on to be passed on to

offspring offspring

Phenotypic TreatmentsPhenotypic Treatments

Symptoms of many genetic disorders can be Symptoms of many genetic disorders can be

minimized or suppressed byminimized or suppressed by

Dietary controlsDietary controls

Adjustments to environmental conditionsAdjustments to environmental conditions

Surgery or hormonal treatmentsSurgery or hormonal treatments

Phenykentonuria (PKU)Phenykentonuria (PKU)

Genetic ScreeningGenetic Screening

Large-scale screening programs detect Large-scale screening programs detect affected persons affected persons

Newborns in United States routinely tested Newborns in United States routinely tested for PKUfor PKU

Early detection allows dietary intervention and Early detection allows dietary intervention and prevents brain impairmentprevents brain impairment

Prenatal DiagnosisPrenatal Diagnosis

AmniocentesisAmniocentesis

Chorionic villus samplingChorionic villus sampling

FetoscopyFetoscopy

All methods have some risksAll methods have some risks

Fig. 12-21, p.202

Image on the ultrasound screen Amniocentesis

Fig. 12-22, p.202

Fetoscopy

Preimplantation DiagnosisPreimplantation Diagnosis

Used with in-vitro fertilizationUsed with in-vitro fertilization

Mitotic divisions produce ball of 8 cellsMitotic divisions produce ball of 8 cells

All cells have same genesAll cells have same genes

One of the cells is removed and its genes One of the cells is removed and its genes

analyzedanalyzed

If cell has no defects, the embryo is If cell has no defects, the embryo is

implanted in uterusimplanted in uterus