Genetic Disorders

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

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

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

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

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%

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

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

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 Hypercholesterolemia

Hypercholesterolemia • Treated with medicines like Lipitor, Mevacor, Zocor

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

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

Hemophilia • sex-linked recessive • On 1 of 2 genes producing clotting factor located on the X chromosome • Most Common in males • “Bleeder’s Disease” • Bleeding spontaneously and in joints • Queen Victoria: descendents affected with hemophilia Alexei Romanov

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

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

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 • Mother’s Age 30 – 1 in 1000 • Mother’s Age over 45 – 1 in 25 • Can live until 50s

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)

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

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

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

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.

gametes

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). • 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.

EXTRA!!! • NOT IN NOTES

Cri-du-chat • “Cat’s 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

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

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

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 • Angleman’s: behavior problems, some mental retardation • Deletion of portion of maternal 15

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

Genetic Disorders