Chapter 12Chapter 12

Chromosomes and Human Chromosomes and Human InheritanceInheritance

ObjectivesObjectives

1. Describe how an understanding of chromosomes helps to account for events that compose mitosis and meiosis.

2. Name some ordinary and extraordinary chromosomal events that can create new phenotypes (outward appearances).

3. Understand how changes in chromosome structure and number can affect the outward appear ance of organisms.

4. Distinguish autosomal recessive inheritance from sex-linked recessive inheritance.

ObjectivesObjectives

5. Give examples of each of the above types of inheritance.

6. Discuss how fruit fly experiments have helped us understand chromosomal behavior.

7. Explain how changes in chromosomal number can occur and present an example of such a change.

8. List examples of phenotypic defects and describe how each can be treated.

ObjectivesObjectives

9. Explain how knowing about modern methods of genetic screening can minimize potentially tragic events.

Neurobiological disorders (NBDs) include Neurobiological disorders (NBDs) include schizophrenia, depression, bipolar schizophrenia, depression, bipolar disorder, and autism.disorder, and autism.

Schizophrenia is a neurobiological Schizophrenia is a neurobiological disorder (1 of every 100 people)disorder (1 of every 100 people)

Symptoms: delusions, hallucinations, Symptoms: delusions, hallucinations, disorganized speech, abnormal social disorganized speech, abnormal social behaviorbehavior

12.0 12.0 Strange Genes, Tortured Strange Genes, Tortured MindsMinds

Emotionally healthy people who show Emotionally healthy people who show creative brilliance tend to have personality creative brilliance tend to have personality traits in common with the mentally traits in common with the mentally impairedimpaired (p186) (p186)

Altered gene expression in certain brain Altered gene expression in certain brain regions may boost creativity as well as regions may boost creativity as well as invite illness (p187)invite illness (p187)

Strange Genes, Richly Tortured Strange Genes, Richly Tortured MindsMinds

12.1 Human Chromosomes 12.1 Human Chromosomes

Some genes on chromosomes control cell Some genes on chromosomes control cell growth and divisiongrowth and division

If something affects chromosome structure If something affects chromosome structure at or near these loci, cell division may at or near these loci, cell division may spiral out of controlspiral out of control

This can lead to cancerThis can lead to cancer

Genes Genes

Units of information about heritable traitsUnits of information about heritable traits

In eukaryotes, distributed among In eukaryotes, distributed among

chromosomes chromosomes

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 Sex chromosomes are nonidentical but still homologous (Human X & Y)still homologous (Human X & Y)

Homologous chromosomes interact, Homologous chromosomes interact, then segregate from one another during then segregate from one another during meiosismeiosis

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 Diploid cell has a pair of alleles at each

locuslocus

Alleles on homologous chromosomes may Alleles on homologous chromosomes may

be same or differentbe same 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

12.2 Karyotype Preparation - 12.2 Karyotype Preparation - Stopping the Cycle Stopping the Cycle

Cultured cells are arrested at metaphase Cultured cells are arrested at metaphase by adding colchicine – a poison that by adding colchicine – a poison that prevents microtubules from forming.prevents microtubules from forming.

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

Karyotype PreparationKaryotype Preparation

Arrested cells are broken openArrested cells are broken open Metaphase chromosomes are fixed Metaphase chromosomes are fixed

and stainedand stained Chromosomes are photographed Chromosomes are photographed

through microscopethrough microscope Photograph of chromosomes is cut Photograph of chromosomes is cut

up and arranged to form karyotype up and arranged to form karyotype diagramdiagram

Fig. 12-3f, p.189

Karyotype DiagramKaryotype Diagram

Philadelphia ChromosomePhiladelphia Chromosome

First abnormal chromosome to be associated First abnormal chromosome to be associated

with a cancerwith a cancer (Spectral Karyotype using (Spectral Karyotype using

colored fluorescent dyes.colored fluorescent dyes.

Reciprocal translocationReciprocal translocation

Causes chronic myelogenous leukemia Causes chronic myelogenous leukemia

(CML)(CML)

12.3 Autosomal 12.3 Autosomal Dominant InheritanceDominant Inheritance

Trait typically Trait typically appears in appears in every every generationgeneration

Fig. 12-10a, p. 190

Huntington DisorderHuntington Disorder

Autosomal dominant alleleAutosomal dominant allele Causes involuntary movements, nervous system Causes involuntary movements, nervous system

deterioration, deathdeterioration, death Symptoms don’t usually show up until person is Symptoms don’t usually show up until person is

past age 30past age 30 People often pass allele on before they know People often pass allele on before they know

they have itthey have it

AchondroplasiaAchondroplasia

Autosomal dominant alleleAutosomal dominant allele In homozygous form usually leads to In homozygous form usually leads to

stillbirthstillbirth Heterozygotes display a type of dwarfismHeterozygotes display a type of dwarfism Have short arms and legs relative to other Have short arms and legs relative to other

body partsbody parts

Autosomal Recessive Autosomal Recessive Inheritance PatternsInheritance Patterns

If parents are If parents are

both both

heterozygous, heterozygous,

child will have a child will have a

25% chance of 25% chance of

being affected being affected

Fig. 12-10b, p. 191

GalactosemiaGalactosemia

Caused by autosomal recessive alleleCaused by autosomal recessive allele Gene specifies a mutant enzyme in the Gene specifies a mutant enzyme in the

pathway that breaks down lactose – may lead pathway that breaks down lactose – may lead to death if not treated.to death if not treated.

galactose-1-phosphate

enzyme 2

lactose galactose

enzyme 1

+glucose

galactose-1-phosphate

enzyme 3

intermediatein glycolysis

12.4 Hutchinson-Gilford 12.4 Hutchinson-Gilford ProgeriaProgeria

Mutation causes accelerated agingMutation causes accelerated aging

No evidence of it running in familiesNo evidence of it running in families

Appears to be dominant (1 out of 8 million Appears to be dominant (1 out of 8 million

births.)births.)

Seems to arise as spontaneous mutationSeems to arise as spontaneous mutation

Usually causes death in early teens Usually causes death in early teens

Sex determination: The Y Sex determination: The Y ChromosomeChromosome

Carries 255 genes, one is the master Carries 255 genes, one is the master

gene for male sex determination gene for male sex determination SRY gene (sex-determining region of Y)SRY gene (sex-determining region of Y)

SRY present, testes formSRY present, testes form

SRY absent, ovaries formSRY absent, ovaries form

The X ChromosomeThe X Chromosome

Carries 1,141 genesCarries 1,141 genes

Most genes deal with nonsexual traits, ex. Most genes deal with nonsexual traits, ex. Blood clotting factors.Blood clotting factors.

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

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 Sex Determination Determination

Thomas Morgan Embryologist – Thomas Morgan Embryologist – discovered sex-linked outcomes of discovered sex-linked outcomes of hemophilia in males.hemophilia in males.

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

Reciprocal crossesReciprocal crosses

12.6 X-linked Inheritance12.6 X-linked Inheritance

Discovering Discovering Linkage Linkage

homozygous dominant female

recessive male

Gametes:

XX X Y

All F1 have red eyes

x

1/4

1/4

1/4

1/4

1/2

1/2 1/2

1/2

F2

generation:

XX X Y

xGametes:

12.7 X-Linked Recessive 12.7 X-Linked Recessive InheritanceInheritance

Males show Males show disorder more disorder more than femalesthan 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 blindness (Red-Green)Color blindness (Red-Green) Inability to distinguish among some of all Inability to distinguish among some of all

colorscolors

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 BlindnessColor Blindness

Fig. 12-11, p.194

HemophiliaHemophilia

Father with Hemophilia and Mother Carrier Genetics

Fragile X SyndromeFragile X Syndrome

An X-linked recessive disorderAn X-linked recessive disorder

Causes mental retardationCauses mental retardation

Mutant allele for gene that specifies a Mutant allele for gene that specifies a

protein required for brain developmentprotein required for brain development

Allele has repeated segments of DNAAllele has repeated segments of DNA

12. 8 Duplication12. 8 Duplication

Gene sequence that is repeated several to Gene sequence that is repeated several to

hundreds of times hundreds of times

Duplications occur in normal Duplications occur in normal

chromosomeschromosomes

May have adaptive advantageMay have adaptive advantage Useful mutations may occur in copyUseful mutations may occur in copy

DuplicationDuplication

normal chromosome

one segment repeated

three repeats

DeletionDeletion

Loss 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

DeletionDeletion

Cri-du-chatCri-du-chat

Fig. 12-13, p.196

InversionInversion

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

within the chromosomewithin the chromosome

segments G, H, I become inverted

In-text figureIn-text figurePage 196Page 196

TranslocationTranslocation

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

Most are reciprocalMost are reciprocal Philadelphia chromosome arose from a Philadelphia chromosome arose from a

reciprocal translocation between reciprocal translocation between chromosomes 9 and 22chromosomes 9 and 22

In-text figurePage 206

TranslocationTranslocation

one chromosome

a nonhomologouschromosome

nonreciprocal translocation

In-text In-text figurefigure

Page 196Page 196

Chromosome StructureChromosome Structure

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

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

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

12.9 Aneuploidy12.9 Aneuploidy

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

(2(2nn + 1 or 2 + 1 or 2nn - 1) - 1) Major cause of human reproductive Major cause of human reproductive

failurefailure Most human miscarriages are Most human miscarriages are

aneuploids aneuploids

PolyploidyPolyploidy

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

Common in flowering plantsCommon in flowering plants Lethal for humansLethal for humans

99% die before birth99% die before birth Newborns die soon after birthNewborns die soon after birth

NondisjunctionNondisjunction

n + 1

n + 1

n - 1

n - 1chromosome alignments at metaphase I

nondisjunction at anaphase I

alignments at metaphase II anaphase II

Figure 12.16Page 198

Down SyndromeDown Syndrome

Trisomy of chromosome 21Trisomy of chromosome 21 Mental impairment and a variety of Mental impairment and a variety of

additional defectsadditional defects Can be detected before birthCan be detected before birth Risk of Down syndrome increases Risk of Down syndrome increases

dramatically in mothers over age 35dramatically in mothers over age 35

Fig. 12-17, p.199

Down SyndromeDown Syndrome

Turner SyndromeTurner Syndrome

Inheritance of only one X (XO)Inheritance of only one X (XO) 98% spontaneously aborted98% spontaneously aborted Survivors are short, infertile femalesSurvivors are short, infertile females

No functional ovariesNo functional ovaries Secondary sexual traits reducedSecondary sexual traits reduced May be treated with hormones, surgeryMay be treated with hormones, surgery

Klinefelter SyndromeKlinefelter Syndrome

XXY conditionXXY condition Results mainly from nondisjunction in Results mainly from nondisjunction in

mother (67%)mother (67%) Phenotype is tall malesPhenotype is tall males

Sterile or nearly soSterile or nearly so Feminized traits (sparse facial hair, somewhat Feminized traits (sparse facial hair, somewhat

enlarged breasts)enlarged breasts) Treated with testosterone injectionsTreated with testosterone injections

XYY ConditionXYY Condition

Taller than average malesTaller than average males Most otherwise phenotypically normalMost otherwise phenotypically normal Some mentally impairedSome mentally impaired Once thought to be predisposed to Once thought to be predisposed to

criminal behavior, but studies now criminal behavior, but studies now discreditdiscredit

12.10 12.10 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

Pedigree for PolydactylyPedigree for Polydactyly

I

II

III

IV

V

6 7

12

5,5 6,6

5,5 6,6

5,5 6,6

5,5 6,6

5,5 6,6

5,5 6,6

6,6 5,5

6,6 5,5

5,6 6,7

6,6 6,6*Gene not expressed in this carrier.

*

malefemale

Fig. 12-9b, p. 200

Genetic AbnormalityGenetic Abnormality

A rare, uncommon version of a traitA rare, uncommon version of a trait

PolydactylyPolydactyly

Unusual number of toes or fingersUnusual number of toes or fingers

Does not cause any health problemsDoes not cause any health problems

View of trait as disfiguring is subjectiveView of trait as disfiguring is subjective

Genetic DisorderGenetic Disorder

Inherited conditions that cause mild to Inherited conditions that cause mild to

severe medical problemssevere medical problems

Why don’t they disappear?Why don’t they disappear? Mutation introduces new rare allelesMutation introduces new rare alleles

In heterozygotes, harmful allele is masked, so In heterozygotes, harmful allele is masked, so

it can still be passed on to offspring it can still be passed on to offspring

Genetic Disorders and Genetic AbnormalitiesGenetic Disorders and Genetic Abnormalities

12.11 Phenotypic Treatments12.11 Phenotypic Treatments

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

be minimized or suppressed bybe minimized or suppressed by Dietary controlsDietary controls

Adjustments to environmental conditionsAdjustments to environmental conditions

Surgery or hormonal treatmentsSurgery or hormonal treatments

Genetic ScreeningGenetic Screening

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

Newborns in United States routinely Newborns in United States routinely tested for PKUtested for PKU Early detection allows dietary intervention Early detection allows dietary intervention

and prevents brain impairmentand prevents brain impairment

Prenatal DiagnosisPrenatal Diagnosis

AmniocentesisAmniocentesis

Chorionic villus samplingChorionic villus sampling

FetoscopyFetoscopy

All methods have some risksAll methods have some risks

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