Genetic Disorders

1
Genetic Disorders

• Inherited in different ways
• Gene mutations
• Autosomal / Sex-linked
• Dominant / recessive/ codominant
• Chromosomal mutations
• Too many- trisomy
• Too few- monosomy
• Deletions of large portions of the chromosome

2
Tay Sachs

• Autosomal Recessive
• Lack of enzyme hexosaminidase A (hex A), which
  breaks down fatty acids in brain in nervous
  tissue
• Symptoms begin to appear at 4-6 months
• Developmental delay, loss of motor skills and
  mental functions, blindness, deafness, paralysis,
  non-responsive to the environment
• Death by 5 years
• Found primarily in those descendants of Ashkenazi
  Jews
• 1/30 American Jews carry the gene

3
Cystic Fibrosis

• Autosomal recessive-
• Chromosome 7 - Point mutation stops production
  of a protein in the lungs and pancreas
• Prevents cells from transporting Cl- ions out of
  the cell
• Lung Congestion
• Abnormally thick mucus lining in lungs
• Chronic Bacterial Infections (pneumonia)
• Treated with antibiotics, lung transplant, and
  new genetic engineering treatments
• Northern European descent

4
Albinism

• Autosomal recessive
• On one of many genes controlling pigment
  production
• Lack of pigment in the skin, hair, and eyes

5
Phenylketonuria (PKU)

• Autosomal recessive- Chromosome 12
• Do not contain enzyme phenylalanine hydroxlyase
  (PAH) that breaks down amino acid phenylalanine
  into amino acid tyrosine
• Phenylalanine builds up in brain
• Toxic to central nervous system (CNS)
• Learning Difficulties, seizures
• Tested at birth
• PKU 1/10,000
• U.S. ? 1/50 carry PKU allele
• Regulated by Strict diet
• Low protein no meat, eggs, dairy
• No Aspartame sugar substitute sold as Equal or
  NutraSweet
• Contains amino acid phenylalanine 50

6
Achondroplasia

• Autosomal dominant
• 1 of 6 kinds of Dwarfism (each has different
  characteristics
• Normal torso length with shortened limbs
• Most common form of dwarfism
• Homozygous dominant zygotes will miscarry

7
Huntington's Disorder

• Autosomal Dominant- chromosome 4
• Lethal due to degeneration of brain cells
• Symptoms onset around ages 35-50
• Lose control over muscles causing uncontrolled
  movements, loss of intellectual faculties, and
  emotional disturbance

8
Hypercholesterolemia

• Familial high cholesterol
• Autosomal codominant on Chromosome 19
• Cells have reduced ability to remove cholesterol
  (lipids) from the blood which causes a build up
  in the arteries (called atherosclerois)
• Blockage leads to early age heart attacks

9
Hypercholesterolemia

• Treated with medicines like Lipitor, Mevacor,
  Zocor

10
Sickle Cell Anemia

• Autosomal Codominant
• Defective Hemoglobin on RBCs caused by 1
  nucleotide base deletion ? shape change
• Damage to brain, heart, lungs
• Carriers are protected from malaria
• African descent 1/10 African Americans in US is
  a carrier

11
Holandric Traits

• Holandric Traits genes on the y chromosome
  carry genes for male sexual characteristics
• Absence of these genes causes female development
• Small arm of y chromosome responsible for
  individuals that have a sex chromosome
  combination that does not match their appearance
• XX males and XY females due to absence or
  presence of SRY factor
• Ghengis Khan
• Mongolian warrior 13th century
• 8 of men living in region that was once
  Mongolian empire have same y chromosome

12
Hemophilia

• sex-linked recessive
• On 1 of 2 genes producing clotting factor located
  on the X chromosome
• Most Common in males
• Bleeders Disease
• Bleeding spontaneously and in joints
• Queen Victoria descendents affected with
  hemophilia

Alexei Romanov
13
Duchenne Muscular Dystrophy

• sex-linked recessive
• Most Common in males
• 1/3500
• Progressive muscle weakening and enlargement
• Dystrophin
• Protein that provides support for the cell
  without it, cell enlarges and explodes

14
Colorblindness

• sex-linked recessive
• On 1 of 3 color vision genes on the X chromosome
• Cannot distinguish between different colors
• Most common type is red/green colorblindness
• Heterozygous female is considered a carrier

• Heterozygous females have mosaic retinas in which
  they have patches of color vision

15
Down Syndrome

• Chromosomal (Autosomal)
• Trisomy 21
• Mild to severe learning disabilities, Distinct
  Facial Features, Heart Defects, low muscle tone
• Most Common Birth Defect 1/700 births
• Mothers Age 30 1 in 1000
• Mothers Age over 45 1 in 25
• Can live until 50s

16
Klinefelter Syndrome

• Chromosomal (Sex chromosomes)
• Trisomy XXY male
• 1 per 1,000 males (most do not know they have an
  extra X chromosome)
• Feminine Characteristics, Sparse facial and body
  hair, dental problems, tall
• Infertile (cannot produce sperm)

17
Turner Syndrome

• Chromosomal (Sex Chromosome)
• Monosomy XO female
• Infertile, Short stature,
• Overweight, Some learning difficulties, Webbed
  Neck, no menstruation
• 1 out of 2,000 live births.
• 96-98 do not survive to birth

18
Edward Syndrome

• Chromsomal (Autosomal)
• Trisomy 18
• Elfin Appearance, Low set ears, Clenched hands,
  Heart disease, Kidney problems, Low birth weight,
  Small head, Small jaw (micrognathia)
• 1 out of 3,000 live births
• 90 die within first 6 months

19
Edward's Syndrome
20
Patau's Syndrome

• Chromsomal (Autosomal)
• Trisomy 13
• Cleft Lip and Palate, Polydactyly, Cleft lip or
  palate, Close-set eyes (eyes may actually fuse
  together into one), Low-set ears, Severe learning
  difficulties, Seizures. Small eyes, Small head
• 1 in 10,000 births
• 80 die within first month

21
Chromosomal Disorders

• Remember that meiosis is the reductional cell
  division that divides one diploid cell to produce
  four haploid gametes (sex cells, sperm or egg).
  Normally gametes have one copy of each
  chromosome.
• Sometimes chromosomes might not separate properly
  during meiosis this is called nondisjunction.
• If nondisjunction occurs, abnormal numbers of
  chromosomes (usually one is missing or there is
  an extra copy of one) are found in gametes and
  disorders of chromosomal numbers may result.

22
gametes
23

1. Trisomy Some chromosomal disorders are caused
   by having three copies of one chromosome. This
   is called trisomy. In trisomies, the gamete of
   one parent donated two of one type of chromosome
   to the child and the gamete of the other parent
   donated one chromosome (like normal).
2. Monosomy Chromosomal disorders characterized by
   missing one chromosome are called monosomies. In
   monosomies, the gamete of one parent donated one
   chromosome and the other did not donate any.

24
EXTRA!!!

• NOT IN NOTES

25
Marfan's Syndrome
NOT IN NOTES

• Dominant Disorder
• 1/20,000 people
• Believed to be caused by a mutation in the
  fibrillin gene on chromosome 15
• Connective Tissue defects
• Dislocation of lens in eye
• Rupture of aorta (weak vessel walls)
• Arachnodactyly spider fingers
• Elongated body, face
• Pectus Excavatum (caved in chest)

26
Marfan's Syndrome

• Abraham Lincoln?
• Descendents of Lincolns great-great grandfather
  (8th generation) diagnosed with Marfans
• Lincoln could have had a mild form of Marfans
• Should we test Lincolns DNA?

27
Adrenoleukodystrophy

• X-linked recessive
• Most Common in males
• Degradation of myelin sheath surrounding nerves
  (insulation)
• fatty acid build up in the brain
• behavioral changes such as abnormal withdrawal or
  aggression, poor memory, visual loss, learning
  disabilities, seizures, poorly articulated
  speech, difficulty swallowing, deafness

Lorenzos Oil Current News Oil not as
effective as previously thought Cholesterol
lowering drug, Lovastatin seems to work Bone
Marrow Transplants work in some cases Lorenzo
Odone turned 27 on May 29, 2005 (Still completely
paralyzed)
28
X-Inactivation

• Barr Body
• Only in females
• Inactivated X chromosome
• Random whether moms or dads X
• Dark staining mass in nucleus
• Allows for equal genetic expression between males
  and females (both express 1 X)
• X-inactivation
• EX Calico Cat
• Coat color is X-linked recessive
• Large patches of color (Black or orange)
• Not in males because they only have 1 X

29
Mitochondrial DNA

• mDNA inherited strictly from the mother
• 600 bp region that is extremely different in
  unrelated individuals
• Romanovs
• Tsar Nicholas II of Russia murdered during
  Bolshevik Revolution in 1918
• Remains identified by comparing mDNA to maternal
  descendants
• Anna Anderson pretended to be Anastasia
• Proved false by mDNA

30
Cri-du-chat

• Cats Cry Syndrome
• Deletion of a portion of Chromosome 5
• Developmental delay, Moon-shaped face, Heart
  disease, Malformed larynx
• 1 in 216,000 births
• Normal lifespan

31
Aniridia-Wilms Tumor Syndrome
11 Deletion of upper arm Developmental delay,
Blindness, Tumors on kidneys 1 in 50,000,000
births Short lifespan
32
Thirteen Q Deletion Syndrome

• 13 Deletion of lower arm
• Developmental Delay, Malformed face, No thumbs,
  Heart disease
• 1 in 500,000 births
• Short lifespan

33
Triple X Syndrome
Tall stature, Mild facial characteristics
(increased width between eyes and proportionately
smaller head size), learning disabilities, speech
and language delays, poor coordination,
introverted, normal sexual development 1 in
2,500 births Normal lifespan
34
XYY Syndrome
XYY only 23 Trisomy Highly variable
sometimes taller than average, increased risk of
learning disabilities, delayed speech and
language skills, behavioral problems, normal
sexual development 1 in 1,000 males
35
Jacobs Syndrome
?
Normal physicallyNormal mentally Increase in
testosterone More aggressive Normal lifespan
36
Genomic Imprinting

• Genomic Imprinting variation in phenotype
  expression depending on which parent gave the
  chromosome
• Chromosome remembers which parent it came from
• EX Deletion of Chromosome 15
• Prader-Willi uncontrollable eating, diabetes,
  mental retardation
• Deletion of portion of paternal 15
• Anglemans behavior problems, some mental
  retardation
• Deletion of portion of maternal 15

37
Prader-Willi Syndrome
1 in 5,000,000 births46 chromosomes XY97
XX3 15 Deletion of lower arm
38
Prader-Willi Syndrome
Small bird-like head Mentally retarded Respiratory
problems Obesity Short lifespan
39
Eighteen Q Deletion Syndrome
1 in 10,000,000 births 46 chromosomesXY or
XX 18 Deletion of lower arm
40
Eighteen Q Deletion Syndrome
Mentally retarded Heart disease Abnormal hands
and feet Large eyes Large ears Normal lifespan
41
Cat-Eye Syndrome
1 in 1,000,000 births 46 chromosomesXY or
XX 22 Deletion of bottom arm
42
Cat-Eye Syndrome
Fused fingers and toes Mentally retarded Small
jaw Kidney and Heart problems Normal lifespan
43
Four-Ring Syndrome
1 in 10,000,000 births 46 chromosomesXY or
XX 4 Inversion
44
Four-Ring Syndrome
Cleft palate Club feet Testes dont descend Short
lifespan
45
Reproductive Technology

• Invitrofertilization (IVF) test tube babies
• Procedure
• Woman treated with fertility drugs to regulate
  menstrual cycle and develop high quality eggs
• Eggs collected using a needle
• Fertilization occurs in a Petri dish
• Within 72 hours embryos transferred to uterus
• Multiple births often occur
• Artificial Insemination fertilization occurs
  within uterus (in vivo)
• Sperm inserted through a catheter passing
  through the cervix into the uterus

46
Reproductive Technology
47
Ultra Sound

• High frequency sound waves with computer produce
  image
• Locate fetus during amniocentesis and CVS
• Estimate fetal age, sex, twins
• 600 disorders can be diagnosed prenatally
• Spina bifida, heart defects, dwarfism,
  hydrocephalus (water on brain)

48
Ultra Sound
49
3D Ultra Sound
50
Fetal Cells

• Fetal Cells obtained from either amniocentesis
  or chorionic villi sampling (CVS)
• Cultured and a karyotype created to diagnose
  genetic disorders
• Alphafetoproteins (AFP) levels indicated in
  sample different levels signal defects
• Low AFP levels
• Downs Syndrome
• High AFP levels
• Spina Bifida spinal cord not contained within
  spinal column
• Twins

51
Genetic Screening

• Genetic Screening a person with family history
  for genetic disorders are screened before
  deciding to have children
• Karyotype of individual created to check for any
  chromosomal abnormalities
• Genetic Counseling couples at risk for having
  children with genetic disorder seek medical
  guidance to determine their chances of having a
  child with a disorder
• Punnett Squares

52
Amniocentesis

• Needle removes small amount of amniotic fluid
  from sac surrounding baby
• 14th 16th week
• Fetal cells and proteins are analyzed
• Karyotype

53
Chorionic Villi Sampling (CVS)

• Through cervix and vagina, remove sample of
  chorion (tissue between uterus and placenta)
• Same DNA as baby
• 8th 10th week
• Fast results since cells grow faster
• Dangerous to fetus

54
Preimplantation Genectic Diagnosis (PGD)

• Identify embryos that do not carry gene for
  inherited disease
• Cystic Fibrosis, sickle cell anemia
• Reduces the risk diseases are passed on to
  children
• Genetic Analysis of one cell from embryo before
  implantation
• Biopsied with needle under microscope doesnt
  harm development of healthy fetuses (cells
  blastomeres)
• Only healthy embryos implanted some are saved
  for later use
• DOES NOT ALTER genetic material
• DOES NOT always occur prior to in vitro
• PGD for X-Linked sex determination
• Only not at risk females are implanted
• Gender selection and family balancing
• Check for Huntingtons disease, CF, chromosomal
  translocation when one parent has a translocation
  and they cause miscarriages in those babies
  produced

55
PGD
56
Sources Pictures

• http//www.mcah.columbia.edu/dbcourses/riseofciv/l
  arge/GREGOR_MENDEL.jpg (Gregor Mendel)
• http//images.google.com/imgres?imgurlhttp//io.u
  winnipeg.ca/simmons/1115/cm1503/Image216.gifimgr
  efurlhttp//io.uwinnipeg.ca/simmons/1115/cm1503/
  mendel.htmh600w408sz101tbnidkuT2IygxnFwJ
  tbnh133tbnw90hlenstart4prev/images3Fq3D
  gregor2Bmendel26svnum3D1026hl3Den26lr3D
  (Pea Plants)
• http//images.google.com/imgres?imgurlhttp//www.
  ri.net/schools/Narragansett/NHS/PerEwebpage/lwf1.J
  PGimgrefurlhttp//www.ri.net/schools/Narraganset
  t/NHS/PerEwebpage/flowere.htmlh538w344sz14t
  bnidk23bBckH-AwJtbnh130tbnw83hlenstart5
  prev/images3Fq3Dflower2Bstructure26svnum3D10
  26hl3Den26lr3D (Flower Diagram)
• http//images.google.com/imgres?imgurlhttp//www.
  synapses.co.uk/genetics/snap1.gifimgrefurlhttp/
  /www.synapses.co.uk/genetics/ssg14.htmlh289w28
  4sz5tbnid1lEcYZJKXbIJtbnh110tbnw108hlen
  start4prev/images3Fq3Dincomplete2Bdominance
  26svnum3D1026hl3Den26lr3D (Incomplete
  Dominance)
• http//images.google.com/imgres?imgurlhttp//www.
  equusite.com/articles/basics/colors/images/basicsC
  olorsRedRoan.jpgimgrefurlhttp//www.equusite.com
  /articles/basics/colors/colorsRoan.shtmlh225w1
  50sz14tbnidg_vyrPiu8fYJtbnh102tbnw68hle
  nstart1prev/images3Fq3Droan2Bhorse26svnum
  3D1026hl3Den26lr3D (Roan horse)
• http//fig.cox.miami.edu/cmallery/150/mendel/sf10
  x9.jpg (Dihybrid Cross)
• http//images.google.com/imgres?imgurlhttp//www.
  nps.gov/abli/hrs/images/fig3.jpgimgrefurlhttp//
  www.nps.gov/abli/hrs/hrst.htmh299w250sz10tb
  nidKYz5-pMLQk8Jtbnh111tbnw92hlenstart17
  prev/images3Fq3Dabraham2Blincoln26svnum3D10
  26hl3Den26lr3D (Lincoln)
• http//images.google.com/imgres?imgurlhttp//gslc
  .genetics.utah.edu/units/basics/blood/images/ABObl
  oodsystem.gifimgrefurlhttp//gslc.genetics.utah.
  edu/units/basics/blood/types.cfmh285w489sz43
  tbnidoByv1TZ9keIJtbnh74tbnw127hlenstart
  4prev/images3Fq3Dblood2Btypes26svnum3D1026
  hl3Den26lr3D26sa3DN (Blood Types)
• http//images.google.com/imgres?imgurlhttp//www.
  retinaaustralia.com.au/images/autodom.gifimgrefur
  lhttp//www.retinaaustralia.com.au/RP.htmh511w
  565sz18tbnid65qX-5yyuywJtbnh118tbnw131h
  lenstart10prev/images3Fq3Dx-linked2Binheri
  tance26svnum3D1026hl3Den26lr3D (x-linked
  inheritance)
• http//images.google.com/imgres?imgurlhttp//www.
  theage.com.au/ffximage/2004/03/05/romanovs.jpgimg
  refurlhttp//www.theage.com.au/articles/2004/03/0
  3/1078295443880.html3Ffrom3Dstoryrhsh220w200
  sz15tbnidGJ_cftXBebIJtbnh102tbnw92hlen
  start1prev/images3Fq3Dromanovs26svnum3D102
  6hl3Den26lr3D (romanovs)
• http//wappingersschools.org/RCK/staff/teacherhp/j
  ohnson/visualvocab/nondisjunction.gif
  (Nondisjuntion)
• http//medstat.med.utah.edu/block2/biochem/Formosa
  /Figures/Lecture5/5-0220Mutations.GIF
  (Mutations)
• http//www.bio.miami.edu/dana/250/sicklecell.jpg
  (Sickle Cell)
• http//www.lrc.edu/summeracademy3/sa18/blood_typin
  g_reactions.jpg (Blood Typing)
• http//www.genomenewsnetwork.org/articles/2004/05/
  28/optics.php (Colorblindness Retina)
• http//www.futura-sciences.com/img/y_chromosome.jp
  g (Y Chromosome)
• http//www.hforhealth.com/images/040705/43469_400.
  jpg (Hemophilia Punnett Square)
• http//images.google.com/imgres?imgurlhttp//www.
  azer.com/aiweb/categories/magazine/73_folder/73_ph
  otos/73_306.jpgimgrefurlhttp//www.azer.com/aiwe
  b/categories/magazine/73_folder/73_articles/73_hem
  ophilia.htmlh252w149sz5tbnidFhjIX7MofY0J
  tbnh106tbnw62hlenstart8prev/images3Fq3D
  hemophilia26svnum3D1026hl3Den26lr3D
  (Hemophilia Knee)
• http//images.google.com/imgres?imgurlhttp//www.
  ikm.jmu.edu/Buttsjl/ISAT493/Hemophilia/QueenVictor
  ia.gifimgrefurlhttp//www.ikm.jmu.edu/Buttsjl/IS
  AT493/Hemophilia/europeanroyalfamily.htmlh539w
  1119sz15tbnid304yBRicLzIJtbnh72tbnw150hl
  enstart7prev/images3Fq3Dhemophilia2Bqueen
  2Bvictoria26svnum3D1026hl3Den26lr3D (Queen
  Victorias Pedigree)

57
Sources Pictures conti.

• http//carnegieinstitution.org/first_light_case/ho
  rn/lessons/images/ (Sickle Cell)
• http//myweb.lsbu.ac.uk/dirt/museum/margaret/68--
  252-3041141.jpg (Cystic Fibrosis Chest Scan)
• http//www.pamspaulding.com/graphics/taysach.jpg
  (Tay Sachs Tissue Sample)
• http//images.google.com/imgres?imgurlhttp//medi
  calimages.allrefer.com/large/marfans-syndrome.jpg
  imgrefurlhttp//health.allrefer.com/pictures-imag
  es/marfans-syndrome.htmlh320w400sz14tbnidy
  2k0kdWMfr8Jtbnh96tbnw120hlenstart1prev/
  images3Fq3Dmarfan2527s2Bsyndrome26svnum3D10
  26hl3Den26lr3D26ie3DUTF-8 (Marfans Diagram)
• www.nlm.nih.gov/.../ ency/esp_imagepages/2927.htm
  (Pectus Excavatum)
• www.civilwardads.com/.../ GettysburgAddress.htm
  (Abraham Lincoln)
• www.biology.iupui.edu/.../ 11nondisjunction.gif
  (Nondisjunction)
• www.bbc.co.uk/.../ mutations3_rev.shtml (Downs
  Syndrome Karyotype)
• bmj.bmjjournals.com/.../ issue7329/twib.shtml
  (Downs Syndrome)
• library.thinkquest.org/ 18258/ped-karyo2.htm
  (Klinefelters Karyotype)
• www.historyplace.com/.../ portraits/presidents/
  (George Washington)
• www.antenataltesting.info/.../ default.html
  (Turners Syndrome Karyotype)
• images.medscape.com/.../ 2002/2155/slide17.gif
  (Turners Syndrome)
• www.angelfire.com/ or3/edwardssyndrome/ (Edwards
  Karyotype)
• livingwithtrisomy13.org/ album11.htm (Pataus
  Syndrome)
• http//medgen.genetics.utah.edu/photographs/diseas
  es/high/cytog005.jpg (Pataus Karyotype)
• www.paulooi.com/wp-content/ June/DSCN0558.JPG
  (Polydactyl)
• www.emedicine.com/ ped/topic504.htm (Cri-du-chat
  karyotype)
• gslc.genetics.utah.edu/. ../criduchat.cfm
  (Cri-du-Chat person)

58
Sex Linkage

• Presence of gene on a sex chromosome (X or y)
• X chromosome is larger than y ? more genes
  carried on the X
• X-Linked Genes genes found on X chromosome
• Appear mostly in males
• Only one copy of X nothing to counteract bad
  gene
• Females would need two copies to express trait