The Nature of Sex

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The Nature of Sex

• Ricki Lewis
• Klug and Cummings

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Platypus Sex Chromosome

• Platypus - Echidna
• Earliest type of mammal duck like bill, web
  feet,fur, and mammary glands
• The platypus, long thought a strange creature,
  just got stranger
• Researchers discovered that it has 10 sex
  chromosomes,
• Some of them linked to mammals and some to birds.

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Evolution of the Sex Chromosomes - Marsupials

• http//www.pubmedcentral.nih.gov/articlerender.fcg
  i?artid53113toolsbot
• http//www.newscientist.com/article.ns?iddn6568

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The Nature of Sex The sex chromosomes in humans
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The Evolution of Y

• The X and Y chromosomes diverged around 300
  million years ago when some reptile, the distant
  ancestor of all mammals, developed a so-called
  'male gene' - simply possessing this gene caused
  the organism to be male.
• The chromosome with this gene became the Y
  chromosome, and a similar chromosome without it
  became the X chromosome.
• So initially, X and Y chromosomes were nearly
  identical. Over time, genes which were beneficial
  for males and harmful to (or had no effect on)
  females either moved to or developed on the Y
  chromosome.

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Recombination between X and Y

• Recombination between the X and Y chromosomes
  proved harmful - it resulted in males without
  necessary genes formerly found on the X
  chromosome
• Females were found with unnecessary or even
  harmful genes previously only found on the Y
  chromosome.
• As a result, genes beneficial to males assembled
  near the sex-determining genes in order to make
  this less probable. Eventually, the Y chromosome
  changed in such a way as to inhibit the areas
  around the sex determining genes from recombining
  at all with the X chromosome.

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The evolution of the Y

• With time, larger and larger areas became unable
  to recombine with the X chromosome.
• This caused its own problems without
  recombination, the removal of harmful mutations
  from chromosomes becomes increasingly difficult.
• These harmful mutations continued to damage
  Y-unique genes until several finally stopped
  functioning and became genetic junk this was
  eventually removed from the Y chromosome.

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More about the Y chromosome

• As a result of this process 95 of the human Y
  chromosome is unable to recombine, the chromosome
  itself contains only 83 working genes
• Compare this to close to 1000 working genes on
  the X chromosome.
• In some animals, Y degradation is even more
  severe. For example, the kangaroo Y chromosome
  contains only the SRY gene

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The Y chromosome

• The Y chromosome has a p and q arm
• The SRY gene bestows the male identity
• The pseudoautosomal region is on the q arm

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Y chromosome

• Short and long arm
• There are 63 pseudoautosomal genes that cross
  over with the X chromosome
• Bulk of the Y chromosome is termed the
  male-specific region or MSY
• The MSY lies between the two pseudoautosomal
  regions

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MSY and Pseudoautosomal genes

• The MSY lies between the two pseudoautosomal
  regions and it consista of three classes of DNA
  sequences
• About 10 to 15 of the MSY consists of X
  transposed sequences that are 99 percent
  identical to counterparts on the X chromosome

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MSY and the other

• The remainder of the MSY contains palindrome
  ridden regions called amplicons
• Most of the MSY genes are vital to fertility

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Y chromosome

• Although 95 of the Y chromosome lies between the
  pseudoautosomal regions, fewer than 80 genes have
  been found here.
• Over half of this region is genetically-barren
  heterochromatin. Of the 80-odd genes found in the
  euchromatin, some encode proteins
• The others encode proteins that appear to
  function only in the testes. A key player in this
  latter group is SRY.

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SRY

• The SRY encodes a transcription factor
• It sends signals to the indifferent gonads early
  in the development of the embryo

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Genes on the Y chromosome

• AMELY (amelogenin,Y-chromosomal)
• ANT3Y (adenine nucleotide translocator-3 on the
  Y)
• ASMTY (which stands for acetylserotonin
  methyltransferase)
• AZF1 (azoospermia factor 1)
• AZF2 (azoospermia factor 2)
• BPY2 (basic protein on the Y chromosome)
• CSF2RY (granulocyte-macrophage colony-stimulating
  factor receptor, alpha subunit on the Y
  chromosome)
• DAZ (deleted in azoospermia)
• IL3RAY (interleukin-3 receptor)
• PRKY (protein kinase, Y-linked)
• RBM1 (RNA binding motif protein, Y chromosome,
  family 1, member A1)
• RBM2 (RNA binding motif protein 2)
• SRY (sex-determining region)
• TDF (testis determining factor)
• TSPY (testis-specific protein)
• UTY (ubiquitously transcribed TPR gene on Y
  chromosome)
• ZFY (zinc finger protein)

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Human Chromosome LaunchPad

• http//www.ornl.gov/sci/techresources/Human_Genome
  /launchpad/chromY.shtml

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Tracing the history of the Y

• indels - insertions into or deletions of the DNA
  at particular locations on the chromosome. One
  insertion particularly useful in population
  studies is the YAP, which stands for "Y
  chromosome alu polymorphism." Alu is a sequence
  of approximately 300 letters (base pairs) which
  has inserted itself into a particular region of
  the DNA. There have been some half a million alu
  insertions in human DNA YAP is one of the more
  recent.
• snips - are "single nucleotide polymorphisms" in
  which a particular nucleotide (an A, for example)
  is changed (perhaps into a G). Stable indels and
  snips are relatively rare and, in the case of the
  latter, so infrequent that it is reasonable to
  assume they have occurred at any particular
  position in the genome only once in the course of
  human evolution. Snips and stable alus have been
  termed "unique event polymorphisms" (UEPs).

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Tracing the history of the Y

• microsatellites are short sequences of
  nucleotides (such as GATA) repeated over and over
  again a variable number of times in tandem. The
  specific number of repeats in a particular
  variant (or allele) usually remains unchanged
  from generation to generation but changes do
  sometimes occur and the number of repeats may
  increase or decrease.

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Tracing the Y

• The fourth polymorphism category is
  minisatellites, extensively studied by Mark
  Jobling at the University of Leicester. Unlike
  microsatellites, in which the repeated sequences
  are short (often no more than 3 or 4
  nucleotides),
• In minisatellites they are normally 10-60 base
  pairs long and the number of repeats often
  extends to several dozen. Changes during the
  copying process take place more frequently in
  minisatellites than in microsatellites and the
  mechanisms may be different in the two cases.

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The Y chromosome and the European Men

• http//www.raceandhistory.com/Science/europeanmen.
  htm

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The X chromosome
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Mammalian comparison
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Unraveling the X
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X Chromosome related genes

• Alport syndrome
• Androgen insensitivity syndrome
• Becker's muscular dystrophy
• Centronuclear myopathy
• Charcot-Marie-Tooth disease
• Coffin-Lowry syndrome
• Duchenne
• Fabry disease
• Fragile X syndrome
• Glucose-6-phosphate dehydrogenase deficiency
• Hemophilia
• Incontinentia pigmenti
• Lesch-Nyhan syndrome
• Menkes disease
• Myotubular myopathy
• Nonsyndromic deafness and X-linked nonsyndromic
  deafness
• Ornithine transcarbamylase deficiency
• Rett syndrome
• Spinal and bulbar muscular atrophy

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X and Y chromosomes

• Genes on the X chromosome are referred to as X
  linked
• Genes on the Y chromosome are referred to as Y
  linked

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X inactivation

• There are two X chromosome in females
• One is inactivated early in embryological
  development
• The inactivation is random so that only one
  chromosome is active in each cell
• Females are mosaics of the X chromosomes

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Barr Body

• The Barr Body is the remnant of the X chromosome

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Calico Cats
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Sex Limited

• Genes that are only expressed in one sex
• Antlers in male deer
• Milk production in female cows

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Sex influenced

• Baldness in males
• Traits that are expressed with one copy in males
  and two copies in females( with hormonal
  influence)

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Genomic imprinting

• The phenomenon of genomic imprinting is the
  differential modification of the maternal and
  paternal genetic contributions to the zygote,
  resulting in the differential expression of
  parental alleles during development and in the
  adult.
• A disturbance in genomic imprinting in humans has
  been shown to play a role in several birth
  defects, genetic diseases and cancers.
• In humans, the most convincing demonstration of
  an imprinted region is at chromosome 15q11-q13
  with a deficiency of the maternal region
  resulting in the Angelman syndrome (AS) and a
  deficiency of the paternal region resulting in
  the Prader-Willi syndrome (PWS).

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Genomic imprinting
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Prader Willi

• short stature
• small hands and feet
• hypotonia and poor muscle development
• excess fat, especially in the central portion of
  the body
• narrow forehead
• almond shaped eyes with thin, down-turned lips
• light skin and hair relative to other family
  members
• lack of complete sexual development in
  adolescence

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Angelman Syndrome
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Angelman Syndrome

• Severe developmental delay (100)
• Minimal use of words or nonverbal receptive
  skills higher than expressive skills (100)
• Movement or balance disorder including, wide
  based gait with feet turned outward, tremulous
  movement of limbs, and uncoordinated movements
  (100)
• Behavioral uniqueness such as frequent laughter
  or smiling, happy demeanor, easily excitable
  often with hand flapping movements, hypermotoric
  behavior (can be seen in infants as ceaseless
  activity), and a short attention span (100)
• Microcephaly by age 2 (gt80)
• Seizures of any type by age 3 years (gt80)
• Abnormal EEG (gt80)
• Strabismus (20-80)
• Tongue thrusting and suck and swallow disorders
  (20-80)
• Feeding problems in infancy (20-80)
• Hypopigmented skin and eyes (20-80)
• Hyperactive tendon reflexes (20-80)
• Uplifted arms when walking (20-80)
• Prominent mandible (20-80)
• Wide mouth/wide spaced teeth (20-80)