matters of sex anueploidy having too many or too few chromosomes compared to a normal genotype...
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MATTERS OF SEXMATTERS OF SEX
Anueploidy Anueploidy having too many or too few chromosomes having too many or too few chromosomes
compared to a normal genotypecompared to a normal genotype MonosomyMonosomy
Possessing only 1 copy of any particular Possessing only 1 copy of any particular chromosomeschromosomes
Monosomy, with the exception of the X Monosomy, with the exception of the X chromosome is incompatable with lifechromosome is incompatable with 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 karyotypesdifferent karyotypes XYXY XOXO both with 1 X chromosomeboth with 1 X chromosome XXXX XXYXXY both with 2 X chromosomesboth with 2 X chromosomes XXXXXX 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 dehydrogenase, gene is carried on the dehydrogenase, gene is carried on the X chromosomeX chromosome
This gene codes for an enzyme that This gene codes for an enzyme that breaks down sugarbreaks down sugar
Females produce the same amount of Females produce the same amount of G6PD enzyme as malesG6PD enzyme as males
XXY 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 sugar
Female could be heterozygous for Female could be heterozygous for G6PD A and G6PD BG6PD A and G6PD B
Each 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 inactive
In 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 expressedexpressed
In 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 cell
Trisomy 21 can not inactivate the extra Trisomy 21 can not inactivate the extra copy of chromosome 21. So you have copy of chromosome 21. So you have Down syndromeDown syndrome
The 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 chromatin Chromosomal regions that possess active genesChromosomal regions that possess active genes
HeterochromatinHeterochromatin These regions stain darker than euchromatinThese regions stain darker than euchromatin Highly repetitive DNA with very few active genesHighly repetitive DNA with very few active genes Usually found around the centromere and near Usually found around the centromere and near
the tips of chromosomes (telomeresthe tips of chromosomes (telomeres))
Facultative HeterochromatinFacultative Heterochromatin Active 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 prevent a portion or an entire chromosome to prevent gene expressiongene expression
X chromosome is made up of facultative X chromosome is made up of facultative heterochromatinheterochromatin
Active X chromosome behaves like Active X chromosome behaves like euchromatin, with active genes that are euchromatin, with active genes that are transcribedtranscribed
Inactive 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 DNA
This inactive DNA makes up the dark This inactive DNA makes up the dark staining Barr bodystaining Barr body
This 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 inactivationinactivation
Consists 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 inactivatedinactivated
4.4. Inactivation is mitotically stableInactivation is mitotically stable 5.5. 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 Chromosomes One 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 chromosomes
Encodes a protein that makes up part Encodes a protein that makes up part of the ribosomeof the ribosome
If 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 ribosomes made and reduce the ribosomes 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 FEMALES In the female fetus future germ cells undergo In the female fetus future germ cells undergo
Lyonization along with somatic cells at the Lyonization 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 gametogenesisduring female gametogenesis
When germ cells develop into oocytes and When germ cells develop into oocytes 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 MALES XXY Klinefelter males also reactivate the XXY Klinefelter males also reactivate the
second X chromosome during gametogenisissecond X chromosome during gametogenisis
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
MOSAICISMMOSAICISM
Is 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 cells
The 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 affected
Some 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 SYNDROME
Newborns may not be affectedNewborns may not be affected Lag behind classmates in sexual Lag behind classmates in sexual
developmentdevelopment Reach puberty they fail to menstruateReach puberty they fail to menstruate Small uterus Small uterus Rudimentary ovariesRudimentary ovaries
Remains a primitive streak gonadRemains a primitive streak gonad SterileSterile
W/O an ovary they can not produce eggs W/O an ovary they can not produce eggs or estrogenor estrogen
TURNER SYNDROMETURNER SYNDROME Can 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 4’11” to 5’2”adult height of 4’11” to 5’2”