Genetic DisordersGenetic Disorders

Inherited in different waysInherited in different ways Gene mutationsGene mutations

Autosomal / Sex-linkedAutosomal / Sex-linked

Dominant / recessive/ codominantDominant / recessive/ codominant Chromosomal mutationsChromosomal mutations

Too many- trisomyToo many- trisomy

Too few- monosomyToo few- monosomy

Deletions of large portions of the chromosomeDeletions of large portions of the chromosome

Autosomal RecessiveAutosomal Recessive Lack of enzyme Lack of enzyme

hexosaminidase A (hex A), hexosaminidase A (hex A), which breaks down fatty acids in which breaks down fatty acids in brain in nervous tissuebrain in nervous tissue

Symptoms begin to appear at 4-Symptoms begin to appear at 4-6 months6 months

Developmental delay, loss of Developmental delay, loss of motor skills and mental motor skills and mental functions, blindness, deafness, functions, blindness, deafness, paralysis, non-responsive to the paralysis, non-responsive to the environmentenvironment

Death by 5 yearsDeath by 5 years Found primarily in those Found primarily in those

descendants of Ashkenazi Jewsdescendants of Ashkenazi Jews 1/30 American Jews carry the 1/30 American Jews carry the

genegene

Autosomal recessive- Autosomal recessive- Chromosome #7 - Point Chromosome #7 - Point

mutation stops production of a mutation stops production of a protein in the lungs and protein in the lungs and pancreaspancreas

Prevents cells from Prevents cells from transporting Cl- ions out of transporting Cl- ions out of the cellthe cell

Lung CongestionLung Congestion Abnormally thick mucus lining Abnormally thick mucus lining

in lungsin lungs Chronic Bacterial Infections Chronic Bacterial Infections

(pneumonia)(pneumonia) Treated with antibiotics, lung Treated with antibiotics, lung

transplant, and new genetic transplant, and new genetic engineering treatmentsengineering treatments

Northern European descentNorthern European descent

AlbinismAlbinism

Autosomal recessiveAutosomal recessive

On one of many genes On one of many genes controlling pigment controlling pigment productionproduction

Lack of pigment in the Lack of pigment in the skin, hair, and eyesskin, hair, and eyes

Autosomal recessive- Chromosome #12Autosomal recessive- Chromosome #12 Do not contain enzyme phenylalanine Do not contain enzyme phenylalanine

hydroxlyase (PAH) that breaks down amino hydroxlyase (PAH) that breaks down amino acid phenylalanine into amino acid tyrosineacid phenylalanine into amino acid tyrosine

Phenylalanine builds up in brainPhenylalanine builds up in brain Toxic to central nervous system (CNS)Toxic to central nervous system (CNS) Learning Difficulties, seizuresLearning Difficulties, seizures

Tested at birthTested at birth PKU – 1/10,000 PKU – 1/10,000

U.S. U.S. 1/50 carry PKU allele 1/50 carry PKU allele Regulated by Strict dietRegulated by Strict diet

Low protein: no meat, eggs, dairyLow protein: no meat, eggs, dairy No Aspartame: sugar substitute sold as Equal No Aspartame: sugar substitute sold as Equal

or NutraSweetor NutraSweet Contains amino acid phenylalanine – 50%Contains amino acid phenylalanine – 50%

AchondroplasiaAchondroplasia

Autosomal dominantAutosomal dominant

1 of 6 kinds of Dwarfism 1 of 6 kinds of Dwarfism (each has different (each has different characteristicscharacteristics Normal torso length with Normal torso length with

shortened limbsshortened limbs Most common form of Most common form of

dwarfismdwarfism Homozygous dominant Homozygous dominant

zygotes will miscarryzygotes will miscarry

Autosomal Dominant- Autosomal Dominant- chromosome #4chromosome #4

Lethal due to Lethal due to degeneration of brain degeneration of brain cells cells

Symptoms onset around Symptoms onset around ages 35-50ages 35-50

Lose control over Lose control over muscles causing muscles causing uncontrolled uncontrolled movements, loss of movements, loss of intellectual faculties, intellectual faculties, and emotional and emotional disturbance disturbance

HypercholesterolemiaHypercholesterolemia

Familial high cholesterolFamilial high cholesterol

Autosomal codominant Autosomal codominant on Chromosome #19on Chromosome #19

Cells have reduced ability Cells have reduced ability to remove cholesterol to remove cholesterol (lipids) from the blood (lipids) from the blood which causes a build up which causes a build up in the arteries (called in the arteries (called atherosclerois)atherosclerois)

Blockage leads to early Blockage leads to early age heart attacksage heart attacks

HypercholesterolemiaHypercholesterolemia

Treated with medicines like Lipator, Treated with medicines like Lipator, Mevacor, ZocorMevacor, Zocor

Autosomal Codominant Autosomal Codominant Defective Hemoglobin on Defective Hemoglobin on

RBCs caused by 1 RBCs caused by 1 nucleotide base deletion nucleotide base deletion shape change shape change

Damage to brain, heart, Damage to brain, heart, lungslungs

Carriers are protected from Carriers are protected from malariamalaria

African descent; 1/10 African descent; 1/10 African Americans in US is African Americans in US is a carriera carrier

Presence of gene on a Presence of gene on a sex chromosome (X or sex chromosome (X or y)y)

X chromosome is larger X chromosome is larger than y than y more genes more genes carried on the Xcarried on the X

X-Linked Genes:X-Linked Genes: genes genes found on X chromosomefound on X chromosome

Appear mostly in males Appear mostly in males Only one copy of X; Only one copy of X;

nothing to counteract nothing to counteract “bad gene”“bad gene”

Females would need Females would need two copies to express two copies to express traittrait

Holandric Traits:Holandric Traits: genes on the y chromosome; genes on the y chromosome; carry genes for male sexual characteristicscarry genes for male sexual characteristics Absence of these genes causes female Absence of these genes causes female

developmentdevelopment Small arm of y chromosome responsible for Small arm of y chromosome responsible for

individuals that have a sex chromosome individuals that have a sex chromosome combination that does not match their combination that does not match their appearanceappearanceXX males and XY females due to absence XX males and XY females due to absence

or presence of SRY factoror presence of SRY factor Ghengis KhanGhengis Khan

Mongolian warrior 13Mongolian warrior 13thth century century8% of men living in region that was once 8% of men living in region that was once

Mongolian empire have same y Mongolian empire have same y chromosomechromosome

sex-linked recessivesex-linked recessive On 1 of 2 genes On 1 of 2 genes

producing clotting producing clotting factor located on the X factor located on the X chromosomechromosome

Most Common in malesMost Common in males ““Bleeder’s Disease”Bleeder’s Disease” Bleeding spontaneously Bleeding spontaneously

and in jointsand in joints Queen Victoria: Queen Victoria:

descendents affected descendents affected with hemophilia with hemophilia

sex-linked recessivesex-linked recessive Most Common in malesMost Common in males

1/35001/3500 Progressive muscle Progressive muscle

weakening and weakening and enlargementenlargement

DystrophinDystrophin Protein that provides Protein that provides

support for the cell; support for the cell; without it, cell enlarges without it, cell enlarges and explodesand explodes

sex-linked recessivesex-linked recessive On 1 of 3 color vision On 1 of 3 color vision

genes on the X genes on the X chromosomechromosome

Cannot distinguish Cannot distinguish between different between different colorscolors

Most common type is Most common type is red/green red/green colorblindnesscolorblindness

Heterozygous female Heterozygous female is considered a carrieris considered a carrier

Chromosomal Chromosomal (Autosomal)(Autosomal)

Trisomy 21Trisomy 21 Mild to severe learning Mild to severe learning

disabilities, Distinct Facial disabilities, Distinct Facial Features, Heart Defects, Features, Heart Defects, low muscle tonelow muscle tone

Most Common Birth Most Common Birth Defect – 1/700 birthsDefect – 1/700 births

Mother’s Age 30 – Mother’s Age 30 – 1 in 10001 in 1000

Mother’s Age over 45 – Mother’s Age over 45 – 1 in 251 in 25

Can live until 50sCan live until 50s

Chromosomal (Sex Chromosomal (Sex chromosomes)chromosomes)

Trisomy XXY maleTrisomy XXY male 1 per 1,000 males (most 1 per 1,000 males (most

do not know they have an do not know they have an extra X chromosome)extra X chromosome)

Feminine Characteristics, Feminine Characteristics, Sparse facial and body Sparse facial and body hair, dental problems, tall hair, dental problems, tall

Infertile (cannot produce Infertile (cannot produce sperm)sperm)

Chromosomal (Sex Chromosomal (Sex Chromosome)Chromosome)

Monosomy XO femaleMonosomy XO female Infertile, Short stature, Infertile, Short stature, Overweight, Some Overweight, Some

learning difficulties, learning difficulties, Webbed Neck, no Webbed Neck, no menstruationmenstruation

1 out of 2,000 live births. 1 out of 2,000 live births. 96-98% do not survive to 96-98% do not survive to

birthbirth

Chromsomal Chromsomal (Autosomal)(Autosomal)

Trisomy 18Trisomy 18 Elfin Appearance, Low Elfin Appearance, Low

set ears, Clenched set ears, Clenched hands, Heart disease, hands, Heart disease, Kidney problems, Low Kidney problems, Low birth weight, Small birth weight, Small head, Small jaw head, Small jaw (micrognathia) (micrognathia)

1 out of 3,000 live births 1 out of 3,000 live births 90% die within first 6 90% die within first 6

monthsmonths

Chromsomal Chromsomal (Autosomal)(Autosomal)

Trisomy 13Trisomy 13 Cleft Lip and Palate, Cleft Lip and Palate,

Polydactyly, Cleft lip or Polydactyly, Cleft lip or palate, Close-set eyes palate, Close-set eyes (eyes may actually fuse (eyes may actually fuse together into one), Low-together into one), Low-set ears, Severe learning set ears, Severe learning difficulties, Seizures. difficulties, Seizures. Small eyes, Small head Small eyes, Small head

1 in 10,000 births1 in 10,000 births 80% die within first month80% die within first month

““Cat’s Cry” SyndromeCat’s Cry” Syndrome Deletion of a portion Deletion of a portion

of Chromosome 5of Chromosome 5 Developmental delay, Developmental delay,

Moon-shaped face, Moon-shaped face, Heart disease, Heart disease, Malformed larynxMalformed larynx

1 in 216,000 births1 in 216,000 births Normal lifespanNormal lifespan

Aniridia-Wilms Tumor SyndromeAniridia-Wilms Tumor Syndrome

#11 Deletion of upper arm#11 Deletion of upper arm

Developmental delay, Developmental delay, Blindness, Tumors on Blindness, Tumors on kidneyskidneys

1 in 50,000,000 births1 in 50,000,000 births

Short lifespanShort lifespan

Thirteen Q Deletion Syndrome

#13 Deletion of lower arm#13 Deletion of lower arm

Developmental Delay, Developmental Delay, Malformed face, No Malformed face, No thumbs, Heart diseasethumbs, Heart disease

1 in 500,000 births1 in 500,000 births

Short lifespanShort lifespan

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

XYY SyndromeXYY 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

Genomic Imprinting: variation in Genomic Imprinting: variation in phenotype expression depending phenotype expression depending on which parent gave the on which parent gave the chromosomechromosome Chromosome “remembers” which Chromosome “remembers” which

parent it came fromparent it came from EX:EX: Deletion of Chromosome 15 Deletion of Chromosome 15 Prader-Willi: uncontrollable eating, Prader-Willi: uncontrollable eating,

diabetes, mental retardationdiabetes, mental retardationDeletion of portion of paternal 15Deletion of portion of paternal 15

Angleman’s: behavior problems, some Angleman’s: behavior problems, some mental retardationmental retardationDeletion of portion of maternal 15Deletion of portion of maternal 15