MATTERS OF SEXMATTERS OF SEXAnueploidyAnueploidy

having too many or too few chromosomes having too many or too few chromosomes compared to a normal genotypecompared to a normal genotype

MonosomyMonosomyPossessing only 1 copy of any particular Possessing only 1 copy of any particular chromosomeschromosomes

MonosomyMonosomy, with the exception of the X , with the exception of the X chromosome is chromosome is incompatableincompatable with lifewith life

X chromosome dosageX chromosome dosage

How to create equal amount of X How to create equal amount of X chromosome gene products in males and chromosome gene products in males and females?females?

Sex Chromosomes: females XX, males XYGenes on X: females 2 , males 1copy

decrease X gene products by half in females

(e.g. humans called X-inactivation)

X CHROMOSOMESX CHROMOSOMES

This was shown by culturing cells with This was shown by culturing cells with different different karyotypeskaryotypes

XYXY XOXO both with 1 X chromosomeboth with 1 X chromosomeXXXX XXYXXY both with 2 X chromosomesboth with 2 X chromosomesXXXXXX XXXXXXXX both with 3 or more X both with 3 or more X chromosomes chromosomes

Looked at levels of enzymes encoded by the Looked at levels of enzymes encoded by the X chromosomeX chromosome

X LINKED GENEX LINKED GENE

G6PD, glucose 6 phosphate G6PD, glucose 6 phosphate dehydrogenasedehydrogenase, gene is carried on the , gene is carried on the X chromosomeX chromosomeThis gene codes for an enzyme that This gene codes for an enzyme that breaks down sugarbreaks down sugarFemales produce the same amount of Females produce the same amount of G6PD enzyme as malesG6PD enzyme as malesXXY and XXX individuals produce the XXY and XXX individuals produce the same about of G6PD as anyone elsesame about of G6PD as anyone else

G6PD GENEG6PD GENE

There are variant alleles of the G6PD There are variant alleles of the G6PD genegene

G6PD A G6PD A G6PD BG6PD B

Produce different variants of the Produce different variants of the enzyme, but both break down sugarenzyme, but both break down sugarFemale could be heterozygous for Female could be heterozygous for G6PD A and G6PD BG6PD A and G6PD BEach cell only produces 1 of the 2 Each cell only produces 1 of the 2 forms of the enzymeforms of the enzyme

X CHROMOSOMEX CHROMOSOME

Only 1 X chromosome is active in any Only 1 X chromosome is active in any given cell. The other is inactivegiven cell. The other is inactiveIn some cells the paternal allele is In some cells the paternal allele is expressed expressed In other cells the maternal allele is In other cells the maternal allele is expressedexpressedIn XXX and XXXX females and XXY In XXX and XXXX females and XXY males only 1 X is activated in any given males only 1 X is activated in any given cell the rest are inactivatedcell the rest are inactivated

X CHROMOSOMEX CHROMOSOME

XXX embryo survives because it XXX embryo survives because it inactivates 2 X chromosomes and has inactivates 2 X chromosomes and has only 1 functioning X chromosome in only 1 functioning X chromosome in any given cellany given cellTrisomyTrisomy 21 can not inactivate the extra 21 can not inactivate the extra copy of chromosome 21. So you have copy of chromosome 21. So you have Down syndromeDown syndromeThe only chromosome we can The only chromosome we can inactivate is the X chromosomeinactivate is the X chromosome

Table 12.3

3 TYPES OF CHROMATIN3 TYPES OF CHROMATIN

EuchromatinEuchromatin true chromatintrue chromatinChromosomal regions that possess active genesChromosomal regions that possess active genes

HeterochromatinHeterochromatinThese regions stain darker than euchromatinThese regions stain darker than euchromatinHighly repetitive DNA with very few active genesHighly repetitive DNA with very few active genesUsually found around the centromere and near Usually found around the centromere and near the tips of chromosomes (telomeresthe tips of chromosomes (telomeres))

Facultative HeterochromatinFacultative HeterochromatinActive like euchromatin in some cells and inactive Active like euchromatin in some cells and inactive like heterochromatin in other cellslike heterochromatin in other cells

Facultative HeterochromatinFacultative Heterochromatin

Serves as a mechanism for a cell to shut off Serves as a mechanism for a cell to shut off a portion or an entire chromosome to a portion or an entire chromosome to prevent gene expressionprevent gene expressionX chromosome is made up of facultative X chromosome is made up of facultative heterochromatinheterochromatinActive X chromosome behaves like Active X chromosome behaves like euchromatin, with active genes that are euchromatin, with active genes that are transcribedtranscribedInactive X chromosome behaves like Inactive X chromosome behaves like heterochromatinheterochromatin

Facultative HeterochromatinFacultative Heterochromatin

The cell inactivates one X chromosome The cell inactivates one X chromosome by converting the entire chromosome by converting the entire chromosome to heterochromatin or inactive DNAto heterochromatin or inactive DNAThis inactive DNA makes up the dark This inactive DNA makes up the dark staining Barr bodystaining Barr bodyThis process occurs in females or any This process occurs in females or any individual with more than one X individual with more than one X chromosomechromosome

LYON HYPOTHESISLYON HYPOTHESIS

1961 English geneticist Mary Lyon 1961 English geneticist Mary Lyon proposed this hypothesis to describe X proposed this hypothesis to describe X inactivationinactivationConsists of 5 tenantsConsists of 5 tenants

1. Condensed X chromosome is 1. Condensed X chromosome is genetically inactivegenetically inactive

2. X inactivation in humans occurs early in 2. X inactivation in humans occurs early in development when embryo consists of development when embryo consists of about 32 cells. 1 or 2 days following about 32 cells. 1 or 2 days following fertilizationfertilization

5 TENANTS OF LYON HYPOTHESIS5 TENANTS OF LYON HYPOTHESIS

3.3. At this stage in each of the 32 cells At this stage in each of the 32 cells one of the X chromosomes is randomly one of the X chromosomes is randomly inactivatedinactivated4.4. Inactivation is Inactivation is mitoticallymitotically stablestable5.5. Net effect of this is to equalize Net effect of this is to equalize phenotypes in males and females for phenotypes in males and females for genes that are carried on the X genes that are carried on the X chromosomechromosome

Human ChromosomesHuman ChromosomesOne X chromosome in females is One X chromosome in females is inactivated early in embryonic inactivated early in embryonic development.development.

PAR REGION NOT INACTIVATEDPAR REGION NOT INACTIVATED

RSP4 gene in this region present on RSP4 gene in this region present on both X and Y chromosomesboth X and Y chromosomesEncodes a protein that makes up part Encodes a protein that makes up part of the ribosomeof the ribosomeIf this gene were inactivated it would If this gene were inactivated it would reduce by half the number of reduce by half the number of ribosomesribosomes made and reduce the made and reduce the protein synthesized capacity of that cell protein synthesized capacity of that cell by halfby half

X REACTIVATION IN FEMALESX REACTIVATION IN FEMALESIn the female fetus future germ cells undergo In the female fetus future germ cells undergo LyonizationLyonization along with somatic cells at the along with somatic cells at the 32 cell stage32 cell stage

Following differentiation of female fetus, the Following differentiation of female fetus, the inactivated X chromosomes are reactivated inactivated X chromosomes are reactivated during female during female gametogenesisgametogenesis

When germ cells develop into When germ cells develop into oocytesoocytes and and enter meiosis their inactivated X enter meiosis their inactivated X chromosomes become reactivated so that chromosomes become reactivated so that every egg produced has an activated X every egg produced has an activated X chromosome prior to fertilizationchromosome prior to fertilization

X REACTIVATION IN MALESX REACTIVATION IN MALESXXY XXY KlinefelterKlinefelter males also reactivate the males also reactivate the second X chromosome during second X chromosome during gametogenisisgametogenisis

The presence of an extra X chromosome The presence of an extra X chromosome during early puberty causes death of male during early puberty causes death of male germ cells and testicular atrophygerm cells and testicular atrophy

This leads to low levels of testosteroneThis leads to low levels of testosterone

NONDISJUNCTION OF SEX CHROMOSOMES

• Extra copies of the X and Y chromosomes do not cause the severe problems that extra autosomes do

• Nondisjunction in mother would produce eggs that are XX or O with no X chromosome

• If XX egg fertilized with X sperm get an individual who is XXX.

• Individual will be sterile and have 2 Barr bodies

NONDISJUNCTION OF SEX CHROMOSOMES

• If XX egg fertilized with Y sperm get an individual who is XXY.

• Individual will be sterile male with many female body characteristics.

• Known as Klinefelter syndrome• Occurs 1/500 male births• If O egg fertilized by Y sperm the zygote is non-

viable• If O egg fertilized by X sperm get and individual

who is XO. Turner syndrome

NONDISJUNCTION OF SEX CHROMOSOMES

• Turner syndrome• Occurs 1/2000 live births• Sterile• Can also have non-disjunction of the Y

chromosome in males• Produce sperm with 2 Y chromosomes• Fertilize an X egg develop into XYY male• Fertile males• Occurs 1/1000 males

MOSAICISMMOSAICISMIs due to a mitotic loss of 1 X Is due to a mitotic loss of 1 X chromosome in a cell early in zygotic chromosome in a cell early in zygotic development development This produces a combination of both This produces a combination of both XX and XO cellsXX and XO cellsThe more XO cells an individual has the The more XO cells an individual has the more severely she will be affectedmore severely she will be affectedSome estimates put mosaic Turner Some estimates put mosaic Turner females as high as 60% to 80%females as high as 60% to 80%

TURNER SYNDROMETURNER SYNDROMENewborns may not be affectedNewborns may not be affectedLag behind classmates in sexual Lag behind classmates in sexual developmentdevelopmentReach puberty they fail to menstruateReach puberty they fail to menstruateSmall uterus Small uterus Rudimentary ovariesRudimentary ovaries

Remains a primitive streak gonadRemains a primitive streak gonadSterileSterile

W/O an ovary they can not produce eggs W/O an ovary they can not produce eggs or estrogenor estrogen

TURNER SYNDROMETURNER SYNDROMECan lead fairly normal lives if they receive Can lead fairly normal lives if they receive hormone supplementshormone supplements

Hormones promote breast development and Hormones promote breast development and other secondary sex characteristics if other secondary sex characteristics if administered during pubertyadministered during puberty

Growth hormone adds up to 3 inches of Growth hormone adds up to 3 inches of height. Can mean the difference between an height. Can mean the difference between an adult height of 4adult height of 4’’1111”” to 5to 5’’22””