Sex Linked Inheritance

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Sex Linked Inheritance  

• presented
• by
• Mr. Weerayuth Supiwong
• ID 463020364-2

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Introduction

• A human female, has 23 pair of chromosomes
• A human male, has 22 similar pairs and one pair
  consisting of two chromosomes that are dissimilar
  in size and structure.
• The 23 rd pair in both the sexes is called sex
  chromosomes
• the female, XX. the male, XY

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X-linked diseases

• X-linked diseases are those for which the gene is
  present on the X chromosome.
• X-linked diseases show inheritance patterns that
  differ from autosomal diseases.
• This occurs because males only have one copy of
  the X chromosome (plus their Y chromosome) and
  females have two X chromosomes.
• Because of this, males and females show
  different patterns of inheritance and severity of
  manifestation. While there are both dominant and
  recessive X-linked diseases, there are some
  characteristics that are common to X-linked
  disorders in general

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• X-linked genes are never passed from father to
  son.
• The Y chromosome is the only sex chromosome that
  passes from father to son.
• Males are never carriers if they have a mutated
  gene on the X chromosome, it will be expressed.
• Males are termed hemizygous for genes on the X
  chromosome.
•  

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X-linked dominant

• hereditary pattern in which a dominant gene on
  the X chromosome causes a characteristic to be
  manifested in the offspring.
• X-linked dominant diseases are those that are
  expressed in females when only a single copy of
  the mutated gene is present.
• Very few X-linked dominant diseases have been
  identified (e.g. hypophosphatemic rickets, Alport
  syndrome, diabetes insipidus)
• hypophosphatemic rickets or vitamin D
  resistant rickets gtgtgtlow serum phosphorus,
  skeletal abnormalities
• Alport syndrome, which involves progressive
  hearing loss and progressive kidney problems.

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Characteristics of X-linked dominant diseases
include

• Never passed from father to son.
• Affected males produce only affected females. An
  affected male only has one X chromosome to pass
  on to his daughters
• Affected females produce 50 normal and 50
  affected offspring.. gtgtgtgt heterozygous
• Males are usually more severely affected than
  females. Some X-linked dominant traits may even
  be lethal to males.
• Females are more likely to be affected. Since
  females have 2 X chromosomes, they have 2
  chances to inherit the mutated allele.

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The pattern for the pedigree of X-linked dominant
inheritance
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Alport syndrome

• www.hpcgg.org/.../ information/introduction.htm

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Pattern for inheritance

• Mating A Mating B

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Pattern for inheritance

• Mating A Mating B
• www.boystownhospital.org/. ../xlink_dom.asp

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hypophosphatemic rickets

• www.vh.org/.../PedRadSecTF/ 103196/Image1.html

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Amelogenesis Imperfecta-1

• a-s.clayton.edu/hampikian/ b4201/reportsChap6.html
  
• X-linked dominant
• Gene name Amelogenin, Chromosome location
  Xp22.3-p22.1
• Altered Cellular function Abnormal tooth enamel
• Symptoms Very hard enamel, thin enamel, small
  teeth, and/or rough teeth
• Incidence Rare

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X-linked recessive

• hereditary pattern in which a recessive gene on
  the X chromosome results in the manifestation of
  characteristics in male offspring and a carrier
  state in female offspring
• X-linked recessive diseases are those in which a
  female must have two copies of the mutant allele
  in order for the mutant phenotype to develop.
• Many X-linked recessive disorders are
  well-known, including color blindness,
  hemophilia, and Duchenne muscular dystrophy.

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The pattern for the pedigree of X-linked
recessive inheritance
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•  
• www.tylermedicalclinic.com/ pgd-presentation18...
  

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Pattern of x linked recessive inheritance

• staff.um.edu.mt/ acus1/02Monogenic.htm

www.mdsa.org.za/ images/x-linkedFig03.gif
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Hemophilia

• The blood fails to clot normally
• Lacking a blood clotting factor
  VIII(antihemophilic globulin, AHG),IX
• bleeding from even minor cuts
• in 1,500 newborn males. Most (75) have
  hemophilia A, a lack of clotting factor VIII.
• Hemophilia B- "Christmas Disease" is a defect in
  clotting factor IX.
• Transfusions of fresh whole blood or plasma or
  factor concentrates control bleeding

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Hemophilia A and B. Coagulation system

www.emedicine.com/.../ 14801480ped0962-01.jpg
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Inheritance of hemophilia

• www.hemophilia.ca/ en/images/figure5.gif

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A Pedigree of Hemophilia in the Royal Families of
Europe

• www.people.virginia.edu/ rjh9u/gif/roylhema.gif

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Hemophilia

• www.pathguy.com/ lectures/hemophilia.jpg

www.thecrookstoncollection.com/ Collection/med
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Duchene muscular dystrophy

• www.rehabinfo.net/.../ mcdonald2/ppt/Slide5.JPG

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Typical features of X-linked recessive
inheritance

• Never passed from father to son.
• Males are much more likely to be affected because
  they only need one copy of the mutant allele to
  express the phenotype.
• Affected males get the disease from their mothers
  and all of their daughters are obligate carriers.
  
• Sons of heterozygous females have a 50 chance of
  receiving the mutant allele.
• These disorders are typically passed from an
  affected grandfather to 50 of his grandsons.

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The Marker X syndrome

• Fragile X syndrome (Marker X syndrome ) is a
  genetic condition involving changes in the long
  arm of the X chromosome. It is characterized by
  mental retardation.

Alternative Names Martin-Bell syndrome Marker
X syndrome
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Causes, Risk Factors

• Fragile X syndrome is the most common form of
  inherited mental retardation in males and a
  significant cause in females.
• The inheritance is different from common dominant
  or recessive inheritance patterns.
• A fragile area on the X chromosome tends to
  repeat bits of the genetic code.
• The more repeats, the more likely there is to be
  a problem.
• Boys and girls can both be affected, but because
  boys have only one X chromosome, a single fragile
  X is more likely to affect them more severely.

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Mental retardation

• Mental retardation is described as below-average
  general intellectual function with associated
  deficits in adaptive behavior that occurs before
  age 18.
• Causes of mental retardation are numerous, but a
  specific reason for mental retardation is
  determined in only 25 of the cases.

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Mental retardation

• Failure to adapt normally and grow intellectually
  may become apparent early in life or, in the case
  of mild retardation, not become recognizable
  until school age or later.
• An assessment of age-appropriate adaptive
  behaviors can be made by the use of developmental
  screening tests.
• The failure to achieve developmental milestones
  is suggestive of mental retardation.

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Fragile X Syndrome Symptoms Signs

• Family history of fragile X syndrome, especially
  a male relative
• Mental retardation
• Large testicles (macro-orchidism)
• Large size
• Tendency to avoid eye contact
• Hyperactive behavior
• Large forehead and/or ears with a prominent jaw

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Fragile X Syndrome Symptoms

• www.fragilexohio.org/ images/366_littleguy.gif

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Origin of Fragile-X Syndrome through
slipped-mispair recombination
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• In the F1 generation, a man hemizygous for an
  X-chromosome with a 40-fold CGG repeat marries a
  woman heterozygous for X-chromosomes with 10- and
  30-fold CGG repeats. Their daughter inherits the
  40 CGG repeat from her father, and the 30 CGG
  repeat from her mother. In her germline,
  slipped-mispair recombination results in
  production of eggs with 10- or 60-fold CGG
  repeats. Although the threshold for expression of
  Fragile-X syndrome is 55CGG repeats, because the
  event occurs only in her germline and not in the
  somatic tissues, she does not show the syndrome.
     
• In the F2 generation, the daughter marries a man
  with a 20-fold CGG repeat. One-half of their sons
  will inherit the 60 CGG chromosome and will
  likely show the syndrome, and one-half of their
  daughters will be carriers.  Further slippage of
  the repeat region may occur in the F3 daughter's
  germlines. These daughters may or may not show
  the syndrome themselves the phenotype is
  sex-influenced, with higher penetrance in males
  (80) than females (30), which may be due the
  presence of a 'standard' X-chromosome in
  heterozygous females.

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Inheritance of Fragile-X syndrome.
www.sciencemuseum.org.uk/. ../genes/218.asp
An altered gene on the X-chromosome causes
Fragile-X syndrome. A girl will normally have a
working gene on her other X-chromosome, which
partially makes up for the altered gene, so girls
are usually less severely affected than boys. The
genetic change in Fragile-X is very unusual it
tends to change between parent and child, so
predicting the exact risk of having an affected
child is complicated.
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Inheritance of Fragile-X syndrome

• This picture shows affected men and women  in a
  fragile x pedigree.  Solid colored shapes are
  those that are affected and dotted shapes are
  those that may have mild symptoms, and carry the
  disease.  The percentages on the pedigree show
  the disease rate as the generations progress. 
  The picture was borrowed from Medical Genetics by
  Carey, John C., Jorde, Lynn B., and White,
  Raymond L.
• www.ikm.jmu.edu/.../ shermananticipation.gif

www.ikm.jmu.edu/.../ shermananticipation.gif
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Marker X syndrome

• www.medscape.com/.../ 88/408805/Art-w100.fig5.jpg

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Sex limited traits

• sex linked traits are generally expressed much
  more often in males than in females.
• some traits which affect one sex more than
  another are not necessarily sex linked.
• Examples are cases of sex limited expression
  which might include genes affecting beard growth
  or breast size, and (in cattle), horn growth and
  milk yield.
• These genes have no visible affect in one sex
  because the necessary machinery to express them
  is not present.

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• Sex-limited inheritance
• A trait that appears in only one sex is called
  sex-limited
• .
• This is different from X-linked inheritance,
  which refers to traits carried on the X
  chromosome.
• Sex hormones and other physiologic differences
  between males and females may alter the
  expressivity of a gene.
• For example, premature baldness is an autosomal
  dominant trait, but presumably as a result of
  female sex hormones, the condition is rarely
  expressed in the female, and then usually only
  after menopause.
• Thus, sex-limited inheritance, perhaps more
  correctly called sex-influenced inheritance, is a
  special case of limited expressivity and
  penetrance

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• Sex - limited traits
• ????
• ?????? secondary sexual characteristic ?????
• - ?????? ?????????? ???? ??????
• ??????? ??????????? ???????? ????????????????

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• Sex-influenced traits
• characteristic may appear in both sexes but
  expression of the phenotype differs.
• Example Early balding (pattern baldness) in
  humans. Heterozygous men (b/b) lose their hair
  heteroyzgous women do not have significant hair
  loss.
• Homozygous men or women (b/b) become bald. The
  trait is therefore dominant in men, recessive in
  women. (We used b to designate the mutant
  baldness allele even though the allele is
  dominant in males.)

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Sex-Influenced traits

• ????????????????????????????????????????? gene
  ????????? autosome ???????????????????????????????
  ??????????????????????????????????????
  ???????????????????
• gene B ???? gene ???????????????????????????
  (baldness)
• gene b ???? gene ???????????????????????????
  (nonbaldness)

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Sex-Influenced traits

• biology.clc.uc.edu/ courses/bio105/geneprob.htm

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baldness
images.webmd.com/.../ medical/hw/nr551566.jpg
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References

• Caspena, A. L., Espino, R. R. C. and Laude, R.P.
  1993. Genetics at the population level.
  SEAMEO Regional Center for Graduate study and
  research in Agricuture (SEAMEO SEARCA),
  University of Philipines Los Baños (UPLB).
• http//www.uic.edu/nursing/genetics/Lecture/Types/
  SingleGene/Sex-linked/sexlinked.htm
• http//www.umm.edu/ency/article/002051.htm
• http//www.umm.edu/ency/article/002050.htm
• http//www.people.vcu.edu/nance/pattern4.html
• http//www.medscape.com/.../ 88/408805/Art-w100.fi
  g5.jpg
• http// www.ikm.jmu.edu/.../ shermananticipation.g
  if
• http// www.rehabinfo.net/.../ mcdonald2/ppt/Slide
  5.JPG
• http// www.pathguy.com/ lectures/hemophilia.jpg
• http// www.hpcgg.org/.../ information/introductio
  n.htm

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References

• http//www.boystownhospital.org/parents/info/genet
  ics/xlink_rec.asp
• http//www.geneticsolutions.com/PageReq?id211611
  389
• http//hordeum.msu.montana.edu/Bio102/maternal/Sex
  -Linked20Inheritance.htm
• http//www.hpcgg.org/LMM/HMSCHDSite/information/in
  troduction.htm
• http//ghr.nlm.nih.gov/dynamicImages/understandGen
  etics/inheritance/XlinkRecessiveMother.jpg
• http// www.fragilexohio.org/ images/366_littleguy
  .gif
• http// www.people.virginia.edu/
  rjh9u/gif/roylhema.gif
• http// www.sciencemuseum.org.uk/.
  ../genes/218.asp

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References

• http//www.fragilex.org/html/what.htm
• http//home.coqui.net/myrna/fragile.htm
• http//www.dpo.uab.edu/birmie/frag.htm
• http//www.sc.chula.ac.th/courseware/2305101/sld21
  7.htm
• http//www.sc.chula.ac.th/courseware/2305101/tsld2
  17.htm
• http//www.ucl.ac.uk/ucbhjow/bmsi/bmsi_4.html
• http//www.vh.org/.../PedRadSecTF/
  103196/Image1.html
• http//biology.clc.uc.edu/ courses/bio105/geneprob
  .htm
• http// www.mdsa.org.za/ images/x-linkedFig03.gif