Sex Linked Traits

Sex chromsomes: 1 pair

female = XX male = XY

X chromosome: Y chromosome:larger, more genes male traitsfemale traits distribution of body fatColor vision height genesBlood-clotting hair on earsHair on head

Genotypes Phenotypes

XN XN

XN Xn

Xn Xn

XN Y

Xn Y

Color Blindness: X- linked

normal

carrier

colorblind

normal

colorblind

Are You Color Blind?

Hemophilia: X- linked

X- linked Traits

• Males need only 1 bad allele, females need 2 bad alleles to be expressed

• Males have a greater chance of expressing X-linked traits

Xn Y

XN YXN Xn

Xn YXN Xn

Sex-Chromosomes Switched:

some organisms have female = XY male = XX

birds, moths, butterflies, some reptiles, some fish

Some may use different letters besides X and YChickens: female = WZ male = WW

Other sex-linked disordersOther sex-linked disorders

• Duchenne’s muscular dystrophyDuchenne’s muscular dystrophy

• Some forms of baldnessSome forms of baldness

• Retinitis pigmentosaRetinitis pigmentosa

Predict the phenotype (sex) Predict the phenotype (sex) of the following genotypes:of the following genotypes:

• XXXX

• XYXY

• XXXXXX

• XYYXYY

• XXYXXY

• XOXO

• YOYO

(O = no other sex chrm present)(O = no other sex chrm present)

The X chrm encodes The X chrm encodes proteins we all needproteins we all need

• In females, one of the two X’s is randomly In females, one of the two X’s is randomly inactivated in all somatic cellsinactivated in all somatic cells

• Females are genetic Females are genetic mosaicsmosaics for X-linked for X-linked genesgenes

• Barr body = inactive X chromosomeBarr body = inactive X chromosome

• ––>> Dosage Compensation Dosage Compensation

Do women have more of those proteins?

Why?-because too much of that good stuff would be bad

Calico CatCalico Cat

Is there a human calico cat?

X-linked conditions that show a X-linked conditions that show a partial phenotype in femalespartial phenotype in females

• Calico catCalico cat– Hemizygous males: brown or orange or whiteHemizygous males: brown or orange or white– Het females: alternating patches of colorHet females: alternating patches of color

• Absence of sweat glands Absence of sweat glands – hemizygous males : with few sweat glandshemizygous males : with few sweat glands– het females : alternating patcheshet females : alternating patches

Human somatic cells are Human somatic cells are diploid:diploid:• 46 chromosomes46 chromosomes

– 22 pairs of autosomes (1, 2, … 22)22 pairs of autosomes (1, 2, … 22)– 1 pair of sex chromosomes (XX or XY).1 pair of sex chromosomes (XX or XY).

Human gametes are haploid:Human gametes are haploid: • 23 chromosomes 23 chromosomes

– 1 each of the 22 autosomes1 each of the 22 autosomes– X or YX or Y

• = “haploid set” or “monoploid set”= “haploid set” or “monoploid set”

Euploid, aneuploidEuploid, aneuploid

• A cell that contains a multiple of the A cell that contains a multiple of the haploid set of chromosomes is called haploid set of chromosomes is called euploideuploid..

• Cells that do not contain a multiple of Cells that do not contain a multiple of the haploid set are called the haploid set are called aneuploidaneuploid..

• Aneuploid cells contain missing or Aneuploid cells contain missing or additional chromosomesadditional chromosomes

Common types of Common types of aneuploidyaneuploidy

• Monosomy - only 1 copy of a given Monosomy - only 1 copy of a given chrm in an otherwise diploid cell.chrm in an otherwise diploid cell.

• Trisomy - 3 copiesTrisomy - 3 copies

The most frequent cause of The most frequent cause of aneuploidyaneuploidy

… … is chromosomal is chromosomal nondisjunctionnondisjunction..

Meiosis Error: Meiosis Error: NondisjunctionNondisjunction

• Chrms or chromatids fail to Chrms or chromatids fail to “disjoin” during meiosis“disjoin” during meiosis

• Fertilization produces a zygote Fertilization produces a zygote with monsomy or trisomy.with monsomy or trisomy.

• Risk of nondisjunction increases Risk of nondisjunction increases dramatically with maternal age.dramatically with maternal age.

PolyploidyPolyploidy• Has entire extra sets of chromosomes (3n, 4n, Has entire extra sets of chromosomes (3n, 4n,

etc.)etc.)

• 35% of flowering plants are polyploid, as well 35% of flowering plants are polyploid, as well as several of agricultural value.as several of agricultural value.

• Triploid plants often infertile Triploid plants often infertile – pairing and segregation is disrupted in meiosispairing and segregation is disrupted in meiosis– commercially beneficial (e.g. seedless fruit)commercially beneficial (e.g. seedless fruit)

• In humans, polyploidy is lethal before or In humans, polyploidy is lethal before or shortly after birthshortly after birth

Sex Chromosome Sex Chromosome AneuploidiesAneuploidies• trisomy-X = 47, XXX (female) trisomy-X = 47, XXX (female)

– 0.1% female births0.1% female births

• double-Y = 47, XYY (male) double-Y = 47, XYY (male) 0.1% male 0.1% male birthsbirths

• Klinefelter Syndrome = 47, XXY (male, sterile) Klinefelter Syndrome = 47, XXY (male, sterile) 0.1% male births0.1% male births

• Turner Syndrome = 45, X Turner Syndrome = 45, X (female, sterile) (female, sterile) 0.5% female births0.5% female births

• (45, Y = embryonic lethal)(45, Y = embryonic lethal)

Klinefelter Syndrome = 47, XXY (male, sterile) 0.1% male births

Turner Syndrome = 45, X (female, sterile,do not developSecondary sex characteristics)0.5% female births

•Trisomy of chromosome 21 = most Trisomy of chromosome 21 = most common autosomal (non-sex chrm) common autosomal (non-sex chrm) aneuploidy (1/800 live births).aneuploidy (1/800 live births).

•Approx. 75% of trisomy 21 Approx. 75% of trisomy 21 conceptions are spontaneously conceptions are spontaneously aborted (miscarriages).aborted (miscarriages).

• Down Syndrome = genetic disorder Down Syndrome = genetic disorder due to trisomy 21.due to trisomy 21.

Down syndromeDown syndrome• Mental retardationMental retardation

• Gastrointestinal tract Gastrointestinal tract obstructionobstruction

• Congenital heart defectsCongenital heart defects

• Respiratory infectionsRespiratory infections

• 15-20 X higher risk of 15-20 X higher risk of leukemialeukemia

• Characteristic appearanceCharacteristic appearance

• Research - determine the Research - determine the critical genes on chrm 21 critical genes on chrm 21 responsibleresponsible

Other AneuploidiesOther Aneuploidies• Trisomy 13 - Edward SyndromeTrisomy 13 - Edward Syndrome

(1/10,000 live births)(1/10,000 live births)

• Trisomy 18 - Patau SyndromeTrisomy 18 - Patau Syndrome(1/6,000 live births)(1/6,000 live births)

• 95% affected fetuses spontaneously 95% affected fetuses spontaneously aborted.aborted.

• 90% mortality during first year of life.90% mortality during first year of life.

• All other trisomies and monosomies are All other trisomies and monosomies are embyronic lethals, resulting in embyronic lethals, resulting in spontaneously aborted fetuses.spontaneously aborted fetuses.

Chromosome Chromosome RearrangemeRearrangementsnts

Chrm Abnormalities and Chrm Abnormalities and Pregnancy LossPregnancy Loss

• About 1/3 of human pregnancies are lost About 1/3 of human pregnancies are lost spontaneously after implantationspontaneously after implantation

• Chrm abnormalities are the leading known Chrm abnormalities are the leading known cause of pregnancy losscause of pregnancy loss

• A minimum 10-15% of conceptions have a A minimum 10-15% of conceptions have a chrm abnormalitychrm abnormality

• At least 95% of these conceptions At least 95% of these conceptions spontaneously abortspontaneously abort

Birth DefectsBirth Defects

• Most common cause of infant death in U.S.Most common cause of infant death in U.S.

• 2-3% of babies are born with a recognizable 2-3% of babies are born with a recognizable birth defectbirth defect

• Can be caused by genetic defectsCan be caused by genetic defects– Chrm abnormalityChrm abnormality– Mutation in gene involved in developmentMutation in gene involved in development

• Can be caused by environmentCan be caused by environment– Fetal alcohol syndrome Fetal alcohol syndrome - Rubella- Rubella– ThalidomideThalidomide - Low folic acid- Low folic acid

Chrm RearrangementsChrm Rearrangements

•ReciprocReciprocationation TranslocTranslocalal

•InInrevrevsionsion

•DeltionDeltion

•DuplicDuplicliclicationation

Chrm Rearrangement:Chrm Rearrangement:TranslocationTranslocation

• Interchange of genetic info Interchange of genetic info between non-homologous between non-homologous chrmschrms

• Present in at least 1/500 Present in at least 1/500 peoplepeople

• Probably result from a mistake Probably result from a mistake by the recombination by the recombination machinerymachinery

Reciprocal Translocation between p arms of 1 and 9

telomere

telomere

centromere

Chrm 1

Chrm 9

{q arm

{p arm

This pairing in meiosis I

Chrm 1

Chrm 9

Metaphase plate

Leads to...

These gametes:

NormalCarrier

NormalAneuploid Aneuploid

Chrm Chrm Rearrangement:Rearrangement: InversionInversiongenetic rearrangement in which the genetic rearrangement in which the

order of genes is reversed in a order of genes is reversed in a chromosome segment chromosome segment

ABC

DEFGH

ABC

DGFEH

ChromosomeChromosome InversionsInversions

• As with translocations, genetic As with translocations, genetic information unchanged (except information unchanged (except at/near breakpoints)at/near breakpoints)

• At synapsis (= homologous At synapsis (= homologous pairing), inversion loops formpairing), inversion loops form

• If a crossover (recombination) If a crossover (recombination) occurs in the loop, then two occurs in the loop, then two abnormal chrms resultabnormal chrms result

Chromosome DeletionsChromosome Deletions• Deletions = missing chrm segmentDeletions = missing chrm segment

• Large deletions often lethal (even in heterozygote)Large deletions often lethal (even in heterozygote)

ABC

DEFGH

ABC

DGH

Some Deletion Some Deletion SyndromesSyndromes• Cri-du-chat (del 5p)Cri-du-chat (del 5p)• Wolf-Hirschhorn (del 4p)Wolf-Hirschhorn (del 4p)• Prader-Willi/Angelmann (del 15q11-13)Prader-Willi/Angelmann (del 15q11-13)• Langer-Giedion (del 8q24)Langer-Giedion (del 8q24)• Miller-Dieker (del 17p13.3)Miller-Dieker (del 17p13.3)• DiGeorge Anamoly (del 22q11)DiGeorge Anamoly (del 22q11)• Smith-Magenis (del 17p11.2)Smith-Magenis (del 17p11.2)• Williams (del 7q1)Williams (del 7q1)• Wilms Tumor/Aniridia (del 11p13)Wilms Tumor/Aniridia (del 11p13)

Gene DuplicationsGene Duplications

• Chromosome segment present Chromosome segment present

in multiple copiesin multiple copies

• Provide material for evolutionProvide material for evolution

• Tandem duplications Tandem duplications – repeatedrepeated segments are adjacent segments are adjacent – often result from unequal crossing-overoften result from unequal crossing-over

ABC

DEF

ABC

DEEF

Genomic ImprintingGenomic Imprinting