Download Influence of Sex on Genetics

Influence of Sex
on Genetics
Chapter Six
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
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
Y Chromosome
SRY Gene
• SRY = Sex-determining Region of Y
• A transcription factor (TF)
– TF’s 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
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
XY Females
Much more common than XX males
1. Y has a deletion removing SRY gene
2. Genes that SRY gene activates are
deleted/not responding
3. Genes encoding hormones are
deleted/not responding
4. Structures do not respond to hormones
•
Lacking receptors
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
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
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%
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
– Doesn’t skip generations
Y-Linked Disorders
• Rare because there are only a few genes
• Always inherited from father to son only
• Most common “disorder”?
– Maleness
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
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
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
X-Linked Recessive
X-Linked Dominant
Mitochondrial
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”
X-Inactivation
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)
Calico Cats
• Male cats have one X (inherited from their
mothers) and so can only have two colors
at most
• Female cats have two X’s and so can
have three colors at most
– Because of X-inactivation ends showing
“patches” of colors
– Calico or Tortoiseshell
Traits with “sex differences”
1. X-linked genes
•
Already covered
2. Sex limited traits
•
Affect a trait/phenotype that is only present
in one sex
3. Sex influenced traits
•
Differences in hormones affect gene
4. Imprinted genes
•
Depends on the parent of origin
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
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
Genetic Imprinting
• When parent of origin for a gene affects
the expression/phenotype of that gene
• Specific genes are silenced in either the
mother’s or father’s 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)
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
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 mother’s version and
father’s version is silenced?
– Child shows phenotype
• What if child inherits father’s version and
mother’s version is silenced…
– Child has normal phenotype
• What if gene was not imprinted?
Human Imprinting
• Humans carry an “imprinting cluster” on
chromosome 15q11-13
• If child inherits mutated father’s 15q:
– Prader-Willi Syndrome
• If child inherits mutated mother’s 15q:
– Angelman Syndrome
• Because other allele of 15q is imprinted
child cannot hide these normally recessive
mutations
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
Next Class:
• Read Chapter Seven
• Homework – Chapter Six Problems;
– Review: 1,3,6,7,8,9,10
– Applied:1,4,5,8,910,12