Lesson Overview

1. Lesson Overview 14.2 Human Genetic Disorders

2. From Molecule to Phenotype • How do small changes in DNA molecules affect human traits? • Changes in a gene’s DNA molecules can change the proteins produced by the DNA by altering their amino acid sequences this may directly affect a person’s phenotype. • Ex. Sickle cell anemia

3. Sickle Cell Disease • caused by a defective allele of the oxygen-carrying protein (hemoglobin) in red blood cells. • The defective allele makes hemoglobin less soluble, causing hemoglobin molecules to stick together into long fibers, forcing cells into a distinctive sickle shape, which gives the disorder its name.

4. Sickle Cell Disease • Sickle-shaped cells are more rigid than normal red blood cells. • Sickle-shaped cells tend to get stuck in the capillaries. • If the blood stops moving through the capillaries, damage to cells, tissues, and even organs can result. • http://www.youtube.com/watch?v=9UpwV1tdxcs • http://www.youtube.com/watch?v=BkC5Hf-AKwo

6. Cystic Fibrosis Cystic fibrosis (CF) is prevalent among European ancestry. Most cases result from the loss of a single amino acid—phenylalanine, causing the protein to fold improperly.

7. Cystic Fibrosis • Children with CF have serious digestive problems and produce thick, heavy mucus that clogs their lungs and breathing passageways. • People with one normal copy of the CF allele are unaffected by CF, • Two copies of the defective allele are needed to produce the disorder, which means the CF allele is recessive

10. Huntington’s Disease • Huntington’s disease is caused by a dominant allele for a protein (glutamine) found in brain cells. • Despite intensive study, the reason this protein is found in the brain cells is still not clear. • Symptomsmental deterioration and uncontrollable movements, usually do not appear until middle age.

11. Genetic Advantages Most African Americans today are descended from populations that originally lived in west central Africa, where malaria is common. Malaria is a mosquito-borne infection caused by a parasite that lives inside red blood cells.

12. Genetic Advantages • Individuals with just one copy of the sickle cell allele are generally healthy, and are also highly resistant to the parasite, giving them a great advantage against malaria.

13. Genetic Advantages of Cystic Fibrosis • More than 1000 years ago, the cities of medieval Europe were ravaged by epidemics of typhoid fever. • Typhoid is caused by a bacterium that enters the body through cells in the digestive system. • The protein produced by the CF allele helps block the entry of this bacterium. • Individuals heterozygous for CF would have had an advantage when living in cities with poor sanitation and polluted water, and—because they also carried a normal allele—these individuals would not have suffered from cystic fibrosis.

14. Diploid Cells Cells with 2 sets of chromosomes All normal human cells are diploids except gametes Abbreviated as 2n

15. Haploid Cells • In humans, sperm & egg cells are haploids • They only contain one set of xm; half the # in a diploid • Sperm=n & Egg=n (n + n= 2n)

16. Chromosomal Disorders • What are the effects of errors in meiosis? • The most common error in meiosis nondisjunctionfailure of homologous chromosomes to separate. • nondisjunction literally means “not coming apart.” • Nondisjunction may result in gametes with an abnormal number of chromosomes, which can lead to a disorder of chromosome numbers.

17. Chromosomal Disorders • If two copies autosomes fail to separate during meiosis, an individual may be born with three copies of that chromosome. • This is known as a trisomy, meaning “three bodies.” • The most common form of trisomy, involving three copies of chromosome 21, is Down syndrome, • Characteristics: mild to severe mental retardation and a high frequency of certain birth defects.

18. Chromosomal Disorders • Nondisjunction of the X chromosomes can lead to a disorder known as Turner’s syndrome. • A female with Turner’s syndrome usually inherits only one X chromosome. • Women with Turner’s syndrome are: sterile, which means that they are unable to reproduce. Their sex organs do not develop properly at puberty.

19. Trisomy • Chromosome disorders are the most common cause of first-trimester miscarriage. • Most estimates suggest that at least 50% of all miscarriages are due to chromosomal factors, with some estimates putting the number at 75% or higher. • Trisomies are the most common chromosome-related finding in post-miscarriage testing. • Of all trisomies, trisomy 16 seems to be the most common in humans, occurring in 1% of all pregnancies.

20. Trisomy 16 • A diagnosis of full trisomy 16 would mean that all the cells in the baby's body were affected by trisomy 16. • Full trisomy 16 is incompatible with life and nearly all affected babies are miscarried in the first trimester. • But it is also possible to have mosaic trisomy 16, meaning some of the body's cells are affected and other cells are normal. • It is also possible, in rare cases, to have a pregnancy in which the placental cells have full trisomy 16 or mosaic trisomy 16 even though the baby is chromosomally normal. • Diagnosis: • Full trisomy 16 may be diagnosed as the cause of a miscarriage if parents collect tissue and request chromosomal testing after the loss, but trisomy 16 can also be diagnosed during pregnancy through CVS or amniocentesis.

22. Trisomy 18 • Clenched hands, Crossed legs • Feet with a rounded bottom (rocker-bottom feet) • Low birth weight, Low-set ears • Mental delay, Poorly developed fingernails • Small head (microcephaly) • Small jaw (micrognathia) • Undescended testicle • Unusual shaped chest (pectus carinatum)

23. Trisomy 13 (Patau’s syndrome) • Cleft lip or palate • Clenched hands (with outer fingers on top of the inner fingers) • Close-set eyes -- eyes may actually fuse together into one • Decreased muscle tone • Extra fingers or toes (polydactyly) • Hernias: umbilical hernia, inguinal hernia • Hole, split, or cleft in the iris (coloboma) • Low-set ears • Mental retardation, severe • Scalp defects (missing skin) • Seizures • Single palmar crease • Skeletal (limb) abnormalities • Small eyes • Small head (microcephaly) • Small lower jaw (micrognathia) • Undescended testicle (cryptorchidism)

24. Trisomy 13

25. Trisomy 22 • It is a frequent cause of spontaneous abortion during the first trimester of pregnancy. • Progression to the second trimester and livebirth are rare.

26. Girl with 8 limbs • http://www.youtube.com/watch?v=RCAD3NShK_k • http://www.youtube.com/watch?v=XM82Hs0LEpc

27. Chromosomal Disorders • In males, nondisjunction may cause Klinefelter’s syndrome. • Klinefelter’s syndrome results from having an extra X chromosome. • It usually affects males. • It prevents these individuals from reproducing. • There have been no reported instances of babies being born without an X chromosome, indicating that this chromosome contains genes that are vital for the survival and development of the embryo.

28. XXY-Klinefelter's Syndrome • They are considered to be males • As babies have weak muscles and reduced strength. They may sit up, crawl, and walk later than other infants. • Puberty- don't much testosterone as other boys. • leads to a taller, less muscular body, less facial and body hair, and broader hips than other boys. • As teens-may have larger breasts, weaker bones, and a lower energy level than other boys. • Adulthood-look smilar to males without the condition, although they are often taller. They are also more likely than other men to have certain health problems, such as autoimmune disorders, breast cancer, vein diseases

29. Man with enlarge mammary glands • http://www.youtube.com/watch?v=d1B9j9GhWhs

30. If sex cells were diploids… • The zygote will have 92 xm and will NOT be viable