Genetic Disorders AP Biology

Detecting Genetic Disorders Amniocentesis Chorionic villus sampling Karyotype Sequential Screen (Quad/Triple Screen) Blood Test

Amniocentesis A technique for determining genetic abnormalities in a fetus by the presence of certain chemicals or defective fetal cells in the amniotic fluid, obtained by aspiration from a needle inserted into the uterus.

CVS –sample of embryonic cells taken for chorionic villus (placenta) can be done earlier than amniocentesis and results yielded sooner

Karyotype A method of organizing the chromosomes of a cell in relation to number, size, and type. Taken during METAPHASE of Mitosis.

Karyotype

Normal Male

Normal Female

NON-DISJUNCTION Chromosomes fail to separate properly - can occur during meiosis I (all cells affected) or meiosis II (half cells affected) Aneuploidy - having an abnormal chromosome number Trisomic/TRISOMY - having 3 chromosomes 2n+1 Monosomic - having 1 chromosome 2n-1 Polyploidy - having move than 2 sets of chromosomes Triploidy - (3n) Tetraploidy - (4n) common in plants – usually lethal in animals and humans

Nondisjunction Disorders Down’s Syndrome - Trisomy 21 Edward’s Syndrome - Trisomy 18 Patau’s Syndrome - Trisomy 13 Turner’s Syndrome - X0 Klinefelter’s Syndrome - XXY Super Male - XYY Super Female - XXX

Down’s Syndrome Characteristic facial features, low mental ability, stocky build, sometimes heart defects. Extra copy of chromosome #21 –Trisomy 21

Edward’s Syndrome Trisomy 18 Motor and mental retardation Congenital heart disease Often dies in infancy

Patau’s Syndrome Trisomy 13 Physical abnormalities – cleft palate, polydactaly, microcephaly

Turner Syndrome XO Female missing one X chromosome short stature wide neck with extra skin folds underdevelopment of sex characteristics – may lead to sterility non-disjunction of sex chromosomes

Klinefelter’s Syndrome XXY male with extra X chromosome poor sexual development, may be sterile subnormal mental ability other forms are XXYY, XXXY, XXXXY (additional X’s increase the severity of phenotypes and mental retardation)

Super Male XYY Jacob’s Syndrome Male with extra Y chromosome Very tall, can show violent behavior Prone to acne Impaired fertility Mentally normal

Chromosomal Abnormalities

Short Arm of # 5 Cri – du- chat Cat-like cry Severe physical and mental abnormalities nonlethal

Gene Mutations Point mutations Changes in 1 or a few base pairs in a single gene Substitutions Base-pair insertions or deletions: - Can result in a frameshift mutation alters the ‘reading frame’ of triplets THE FAT CAT ATE … THF ATC ATA TE….

Gene Abnormalities Point Substitution Silent – no change in aa Nonsense – STOP CODON Missense – change in aa THE FAT CAT ATE THE RAT  TOE FAT CAT ATE THE RAT *Insertion/Addition *Deletion *May result in a Frame-Shift Mutation THE FAT CAT ATE THE RAT  THF ATC ATA TET HER AT (ENTIRE MESSAGE SHIFTS) Transposons (jumping genes) – transfer of a gene from one locus to another on a chromosome – may unactivated relocated gene – which may produce a point mutation and could result in the elimination of a vital metabolic pathway

Sickle Cell Anemia Abnormal hemoglobin 1 aa substitution causes abnormality (point mutation) Codominance (carrier) Low oxygen RBC will become crescent shape

Inherited Genetic Disorders Autosomal Dominant Inherit one allele Autosomal Recessive Must inherit two recessive alleles, one from each parent. Parent’s are usually CARRIERS of the disorder Sex-Linked Disorders Usually recessive, inherited on X-chromosome More common in males

Autosomal Dominant Huntington’s Disease Marfan Syndrome Achondroplasia

Huntington’s Disease Autosomal Dominant Disorder (lethal) CNS problem Dementia Impaired memory Asymptomatic until later in life (40)

Marfan Syndrome Autosomal Dominant Connective tissue defect Tall, thin, long arms and legs Enlarged aorta Abe Lincoln did NOT have Marfan Syndrome

Achondroplasia Autosomal Dominant Defects in growth of long bones Form of dwarfism Short arms and legs but torso of normal size, large head compared to body

Autosomal Recessive PKU Albinism Tay Sachs Cystic Fibrosis

PKU Phenylketonuria Autosomal Recessive Lack enzyme to convert phenylalanine to tyrosine Buildup of phenylalanine can cause retardation Test babies at birth Special diet for phenylketonurics

Albinism Lack of pigmentation in skin, hair, eyes Inability to make melanin Autosomal recessive

Tay-Sachs Autosomal recessive Degeneration of nervous system No enzyme to break down lipids in brain cells, so they swell and die (death by age 5) - Lethal High incidence in Ashkenazie Jews Blood test available to potential parents

Cystic Fibrosis Cystic Fibrosis, incurable hereditary disorder that causes the body to secrete an abnormally thick, sticky mucus that clogs the pancreas and the lungs, leading to problems with breathing and digestion, infection, and ultimately, death. Common among Caucasians One of the most common fatal genetic disorders in the United States Lethal Autosomal recessive, caused by missing 3 bases/1 aa (phenylalanine) protein does not fold correctly

Sex-Linked Traits Gene loci on a sex-linked chromosome Genes for many sex-linked traits, unrelated to gender, are found on the X chromosome Follow Mendelian Laws of Inheritance May be either dominant or recessive Hemophilia Duchenne Muscular Dystrophy Colorblindness

Hemophilia Sex-linked recessive disorder Lack of protein necessary for normal blood clotting

Duchenne Muscular Dystrophy Sex-linked recessive disorder Absence of muscle protein dystrophin Progressive muscle deterioration and loss of coordination – most die by age of 20

Colorblindness