Influence of Sex on Genetics

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Influence of Sex on Genetics

• Chapter Six

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Humans

• 23 Autosomes
• Chromosomal abnormalities very severe
• Often fatal
• All have at least one X
• Deletion of X chromosome is fatal
• Males heterogametic sex
• XY
• Females homogametic sex
• XX

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Sex Chromosomes

• Y chromosome
• Contains 90 genes
• Majority of genes Male Specific Region (MSR)
• SRY gene determines maleness
• X chromosome
• Contains 1500 genes
• Some dealing with sexual development
• Most genes encoding proteins that have
• nothing to do with sex

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Y Chromosome
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SRY Gene

• SRY Sex-determining Region of Y
• A transcription factor (TF)
• TFs are genes that control the expression of
  other genes (turn on/off)
• SRY turns on male genes
• Male genes activate male hormones
• Male hormones (testosterone) end up producing
  male structures
• Also, destroy female structures

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Sex Chromosomal Abnormalities

• XX males
• Will be carrying a small piece of Y (crossing
  over) that contains the SRY gene
• XY females
• Deletion of SRY region
• XO Turner Syndrome
• Females short, sterile, lack of female features
• XXY Klinefelter Syndrome
• Males feminization, infertility

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XY Females

• Much more common than XX males
• Y has a deletion removing SRY gene
• Genes that SRY gene activates are deleted/not
  responding
• Genes encoding hormones are deleted/not
  responding
• Structures do not respond to hormones
• Lacking receptors

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Genetics of Homosexuality

• How genetic is any trait?
• Examine sharing trait between relatives who also
  share genes
• MZ vs. DZ twins
• Concordance rate
• Siblings/relatives of individual with trait vs.
  general population
• Trait Prevalence
• Transgenic Animal Models

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Genetics of Homosexuality

• Examine sharing trait between relatives who also
  share genes
• Concordance rate
• 52 MZ vs. 20 DZ twins
• Trait Prevalence
• 9-15 siblings vs. 2-5 general population
• Animal Models
• Fruit flies and honey bees

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For Comparison

• Autism
• 90 MZ concordance vs. 2 DZ
• Relative risk is 50-100 times greater than
  general population risk
• Heritability 90
• Depression
• 46 MZ vs. 20 DZ
• Relative risk is 9 times general population
• Heritability 50

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Autosomal Disorders

• Both Males and Females affected, and both
  transmit to both sexes of offspring
• Recessive usually rare in population
• Skips Generations
• Inbreeding increases risk of recessive traits
• Dominant
• Doesnt skip generations

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Y-Linked Disorders

• Rare because there are only a few genes
• Always inherited from father to son only
• Most common disorder?
• Maleness

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X-Linked Recessive

• Gene on X chromosome is carrying trait
• Recessive
• More males are affected
• Passed from affected mothers to all sons
• Affected fathers will only transmit to
  heterozygous, unaffected daughters
• Very rare to see homozygous recessive females

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X-Linked Dominant

• Gene on X chromosome is carrying trait
• Dominant
• Males and females both affected
• Can be passed to both offspring, however often
  see more females affected because of male
  lethality
• Affected fathers to every single daughter

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Mitochondrial Disorders

• Not to be confused with X-linked disorders, but
  they do show a sex difference
• Affected mothers pass disorder onto every single
  child
• Affected fathers NEVER pass disorder on

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X-Linked Recessive
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X-Linked Dominant
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Mitochondrial
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X-Inactivation

• In order for females to not have 1,500 more genes
  than males have, mammals undergo X-inactivation
• Early in development
• One X randomly inactivated in each cell
• Every cell derived from that 1st cell has same
  identical X inactivated
• Therefore females are mosaics

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X-Inactivation
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Calico Cats

• Cat coat color is on X chromosome
• Alleles
• Tabby (stripes) and white
• Black and white
• Orange/Red and white
• White (actually a recessive trait that lacks any
  other colors)
• Additional genes will control amount, positions
  of colors, and pointing (Siamese)

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Calico Cats

• Male cats have one X (inherited from their
  mothers) and so can only have two colors at most
• Female cats have two Xs and so can have three
  colors at most
• Because of X-inactivation ends showing patches
  of colors
• Calico or Tortoiseshell

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Traits with sex differences

• X-linked genes
• Already covered
• Sex limited traits
• Affect a trait/phenotype that is only present in
  one sex
• Sex influenced traits
• Differences in hormones affect gene
• Imprinted genes
• Depends on the parent of origin

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Sex Limited Traits

• Genes are inherited from both parents
• Either autosomal or X chromosome
• Yet, affect a structure that is only present in
  one sex, therefore phenotype shows a sex
  difference
• Horns
• Milk production
• Genitalia anatomy/function

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Sex Influenced Traits

• Genes are inherited from both parents
• Either autosomal or X chromosome
• Yet the affect of differences in sex hormones
  causes differences in phenotype
• Male pattern baldness
• Often dominant in one sex, and recessive in the
  other

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Genetic Imprinting

• When parent of origin for a gene affects the
  expression/phenotype of that gene
• Specific genes are silenced in either the
  mothers or fathers chromosomes
• If an individual receives a silenced gene the
  individual will not express that allele of the
  gene
• Effectively end up hemizygous (only one copy
  rather than two)

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Genetic Imprinting

• Imprinted gene silenced gene
• Silencing occurs by an epigenetic process
• Epigenetic altering genetics
• Process methylation of the gene
• Adding Methyl groups to the DNA structure
• Does NOT change DNA sequence
• Silences one allele, therefore individual only
  shows phenotype of other allele
• Hemizygous

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Effect of Imprinting

• Imagine a case where an imprinted gene has a
  dominant mutation in the mother, but completely
  normal in the father
• What if child inherits mothers version and
  fathers version is silenced?
• Child shows phenotype
• What if child inherits fathers version and
  mothers version is silenced
• Child has normal phenotype
• What if gene was not imprinted?

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Human Imprinting

• Humans carry an imprinting cluster on
  chromosome 15q11-13
• If child inherits mutated fathers 15q
• Prader-Willi Syndrome
• If child inherits mutated mothers 15q
• Angelman Syndrome
• Because other allele of 15q is imprinted child
  cannot hide these normally recessive mutations

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About Imprinting

• This is a normal process in mammalian embryos
• Function is not exactly known
• Theories are
• Used for exact timing/regulation of development
• Arose in evolution of multi-fathered litters
• Only with mutations do you see detrimental
  effects of imprinting

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Next Class

• Read Chapter Seven
• Homework Chapter Six Problems
• Review 1,3,6,7,8,9,10
• Applied1,4,5,8,910,12