1. TALKIE TIME RECAP

2. Competencies:
Explain sex linkage and recombination - STEM_BIO11/12-IIIa-b-2
2. Differentiate the human genetic disorder - Addendum

3. Sex Determination & Sex-Linked Inheritance & Human Genetic Disorders

4. Most species of animals and plants carry a pair of chromosomes that determine the individuals sex.
These are called sex chromosomes.
All other chromosomes are called autosomal

5. Sex Chromosomes Females have two complementary sex chromosomes: XX
Males have 2 non-complementary sex chromosomes: XY
Blood clotting

6. The Y chromosome The Y chromosome is much smaller than the X.
It carries a small number of genes, most of which are for “male characteristics”

8. X chromosome All human eggs contain the X chromosome.
The X chromosome contains genes that code for all aspects of femaleness and genes unrelated to gender.
Including genes for:
Vision
Immunity

9. Sex-Linked Genes Genes unrelated to gender on the X chromosome.
Females have two X chromosomes (so they can be heterozygous or homozygous for each of these genes)
Males have one copy of the sex-linked genes.
Thus, the male is referred to as hemizygous.

10. Hemophilia A blood disorder where the blood does not clot properly.
A minor cut can cause serious injury and demand medical attention.
Bleeding into the joints, internal bleeding and deep cuts can be fatal for hemophiliacs.
Genetic lack of one of the clotting factors produced by the liver.
There is no cure for hemophilia but treatment options with clotting factor transfusions are available.

12. Complications from hemophilia include: bruising and bleeding into the muscles, bleeding into the joints, infection, adverse reaction to transfusions and serious bleeding.

13. Genetics of Hemophilia
The gene for hemophilia is found on the X chromosome
It is a recessive disorder.
It is referred to as a sex-linked recessive disorder.
Males are more likely to get hemophilia.
Females have the possibility of being heterozygous for hemophilia. (This makes them a carrier)

14. PEDIGREE OF QUEEN VICTORIA

15. Czar Nicholas II & Family

16. Grigori Rasputin

17. In this example: The father has hemophilia
In this example: The father has hemophilia. He cannot give his son hemophilia because he gives his son the Y chromosome.
He can give his daughter the recessive gene, but if her mother does not give her the recessive gene, she will not have hemophilia. She will be a carrier.

18. In this example:
The mother is a carrier of hemophilia.
She does not have hemophilia but she is heterozygous for the trait.
There is a 50% chance her son will have hemophilia.

19. Color Blindness
Males are more likely to be color blind due to the fact they only have one X chromosome.
Color Blindness is a sex-linked trait found on the X chromosome.

20. Red-Green Colorblindness
Red-green colorblindness is caused by an abnormal gene for photoreceptors in the retina
The genes for both red and green photoreceptors are located on the X chromosome – colorblindness can result from recessive alleles for either one or both of these genes

22. In this example: the mother is a carrier of the colorblind gene.
There is a 50% chance her son will be colorblind but unless the father is colorblind the daughter cannot end up colorblind.

23. Sex-Linked Inheritance Punnett Square
In the punnett square the mother is a carrier and the father is normal.
Male offspring: % normal & % hemophiliac
Female offspring: % normal % carrier

24. Complete the following punnett square:
Cross a normal mother with a hemophiliac father.
Results:
Genotypes: 50% %
Phenotypes: 50% %

25. How does a male show a recessive sex-linked trait?
What is the only way for a female to show a recessive sex-linked trait?
She must inherit a recessive trait from both her mother and father. (her father must have the disorder)
How does a male show a recessive sex-linked trait?
He must inherit the recessive trait from his mother. He gets the Y from his father so it has no bearing on a sex-linked disorder.

26. Human Genetic Disorders

27. Genetic Disorders Major types of genetic disorders: Autosomal
Single genes
Multiple genes
Sex-linked
Chromosome abnormalities

28. Autosomal Disorders
Autosomal genetic disorders are caused by alleles on autosomes (chromosomes other than the sex chromosomes)
Most are recessive (need 2 recessive alleles to have the disorder)
People with 1 recessive allele are carriers – they do NOT have the disorder but are able to pass the allele on to their children
Ex: Cystic fibrosis (CF), sickle cell anemia
Can also be dominant (need only 1 allele to have the disorder)
Ex: Huntington’s disease

29. Cystic Fibrosis (CF)
Cystic fibrosis is the most common genetic disorder among white people
1 in 2500 white babies are born with CF (4-5 born every day)
It is estimated that 1 in 20 white people is a carrier for CF

31. Cystic Fibrosis (CF) Caused by an abnormal gene on chromosome 7
The gene is for a protein pump that uses active transport to regulate the movement of sodium (Na+) and chloride ions (Cl-) into and out of cells

32. Cystic Fibrosis (CF)
In healthy individuals, the normal protein allows movement of Na+ and Cl- ions
Keeps mucus thin and easily swept away
With CF, not enough Cl- ions are pumped out
Thickening of mucus in airways and pancreatic ducts

33. Symptoms of CF Buildup of mucus in the lungs/ respiratory system
Difficulty breathing
Infections
Blocks digestive enzymes (produced by the pancreas) from entering the intestine
Malnutrition
Abnormal Na+ transport also results in salty sweat

34. Treatments for CF For respiratory symptoms: For digestive symptoms:
Physical therapy
Breathing exercises
Antibiotics
Lung transplants in severe cases
For digestive symptoms:
Capsules containing pancreatic digestive enzymes
Even with treatment, CF continues to be fatal, but patients live longer and have a higher quality of life

35. Sickle-Cell Anemia (Sickle-Cell Disease)
The most common genetic disorder among black people
About 1 in 500 African Americans has sickle-cell anemia.
Carriers are said to have sickle-cell trait

37. Sickle-Cell Anemia Caused by an abnormal gene on chromosome 11
The gene is for one of the polypeptide chains in hemoglobin, a protein found in red blood cells that is responsible for transporting oxygen through the bloodstream

38. Sickle-Cell Anemia
Sickle-cell anemia causes hemoglobin to clump within red blood cells, which distorts their shape from the normal biconcave disc to a sickle shape.
People with sickle-cell trait have some abnormal hemoglobin but do not have the symptoms of sickle-cell disease.

39. Symptoms of Sickle-Cell Anemia
Abnormal hemoglobin cannot deliver oxygen as efficiently to cells as in healthy individuals
Fatigue
Dizziness
Headaches
Sickled red blood cells cannot move as easily through capillaries as normal RBCs
Chronic pain, especially in bones
Reduced immune response to infections
Strokes

40. Treatments for Sickle-Cell Anemia
Treatments for sickle-cell anemia include:
Blood transfusions
Antibiotics
Drugs that increase oxygen-carrying capacity of RBCs
Drugs that “switch on” the gene for fetal hemoglobin, which is normally switched off after birth
Living with sickle-cell anemia

41. More Autosomal Recessive
Tay Sachs Disease
Fatty substance builds up in neurons
Gradual paralysis and loss of nervous function by age 4-5
Single defective enzyme
Heterozygote carriers (Hh) do not have disorder, but are resistant to Tuberculosis
Especially common in Jewish population (central and eastern European descent), up to 11% are carriers

42. More Autosomal Recessive
PKU (Phenylketonuria)
Can’t break down amino acid phenylalanine (missing critical enzyme)
Phenylalanine builds up and interferes with nervous system leading to mental retardation and even death
Early screening  phenylalanine restricted diet for children with disorder

43. Heterozygote Superiority
Why are cystic fibrosis and sickle-cell anemia so common?
Sickle-cell anemia is most common in areas of the world where malaria is prevalent
Malaria is caused by a parasite that invades red blood cells
These parasites do not thrive in people with abnormal hemoglobin, so people with sickle-cell trait (who are heterozygous) are resistant to malaria.
People who are heterozygous for the cystic fibrosis allele may be more resistant to cholera
When carriers have an advantage over people who are homozygous dominant, it is called heterozygote superiority

45. Huntington’s Disease
Caused by an abnormal dominant allele (unlike most human genetic disorders)
Both men and women need only one Huntington’s allele to get the disorder.

47. Symptoms of Huntington’s Disease
Huntington’s disease affects a person’s brain cells
Clumsiness
Irritability
Depression
Memory loss
Loss of muscle coordination & ability to speak
Symptoms normally appear by age 40
Huntington’s disease is always fatal
Death normally occurs within 20 years of the onset of symptoms
Living with Huntington’s

48. Multiple Genes
Cystic fibrosis, sickle-cell disease, and Huntington’s disease are all caused by mutant alleles for a single gene.
Many other genetic disorders are believed to be the result of multiple genes:
Diabetes mellitus
Heart disease
Some personality disorders
Bipolar disorder, schizophrenia
These are much more complicated to analyze than disorders caused by single genes

49. Diabetes mellitus
Heart disease
Some personality disorders
Bipolar disorder, schizophrenia

50. Chromosome Abnormalities
Autosomal and sex-linked genetic disorders are both caused by certain alleles – small segments of DNA that make up part of a chromosome
Other genetic disorders result from chromosome abnormalities caused by mistakes made during meiosis.
May change the number or structure of chromosomes within gametes

51. 1. Nondisjunction
Nondisjunction is the failure of a pair of chromosomes to separate during meiosis
Results in one gamete having too many chromosomes and the other too few
Trisomy – a zygote gets 3 copies of a chromosome
Monosomy – a zygote gets only 1 copy of a chromosome

52. 2. Translocation
Translocation is when a piece of one chromosome breaks off and attaches to a different chromosome
Often happens to 2 chromosomes at once

53. Karyotypes
Both nondisjunction and translocation can be detected in karyotypes
A karyotype is made from taking individual pictures of all of a human’s chromosomes and matching up homologous pairs

54. Down syndrome
Down syndrome - a genetic disorder caused by chromosome abnormality
Nondisjunction – the person has an extra copy of chromosome 21
Called trisomy 21
Translocation – most of chromosome 21 breaks off during meiosis and fuses with another chromosome, usually #14
This cause of Down syndrome is most likely to occur in children born to mothers over age 40

56. Edward Syndrome Caused by Trisomy 18 Symptoms:
Mental and physical retardation
Skull and facial abnormalities
Defects in all organ systems
Poor muscle tone
Average life expectancy: 2-4 months

57. Patau Syndrome Caused by Trisomy 13 Symptoms:
Mental and physical retardation
Skull and facial abnormalities
Defects in all organ systems
Cleft lip & large triangular nose
Extra digits
Average life expectancy: 6 months (but ½ die in the first month)

58. Sex Chromosome Abnormalities
Turners Syndrome (X0 - female)
1 in 2000
Infertile, sexually underdeveloped, short stature, narrow aorta, normal intelligence
Klinefelter Syndrome (XXY - male)
1 in 1000
Reduced sexual maturity, secondary sexual characteristics (breast swelling), no sperm production

61. Sex Chromosome Abnormalities
Triple X Syndrome (XXX – female)
1 in 1500
Slight IQ reduction, menstrual irregularities
Jacob Syndrome (XYY – male)
Incidence unknown (lack of diagnosis)
Tall, acne issues, speech/reading problems
Disproportionate number incarcerated
96% are normal (most don’t realize they have this condition)

64. DNA Mutations Cri du Chat Syndrome (cry of the cat) Fragile X
Deletion on part of chromosome 5
Fragile X
Repeated sequences of CCG on X chromosome
Normal = 6-50 copies
Carrier (males) = copies
Disorder = more than 230 copies
Causes mental retardation (2nd behind only Down Syndrome)

67. Congenital Disabilities
Congenital disabilities are different from genetic disorders
Not inherited
Occur during fetal development
Both genetic disorders and congenital disabilities can often (but not always) be detected before a baby is born

68. Genetic Counseling
Genetic counseling can help parents determine the likelihood of their child being born with a genetic disorder
Genetic counselors study the family histories of both parents
Create pedigree charts to trace the passage of traits
Medical geneticists analyze blood tests to determine if parents are carriers of certain genetic disorders
Genetic counseling usually can NOT determine whether or not a child will be born with a genetic disorder

69. Diagnosing Genetic Disorders
There are several ways to determine whether a child will have a genetic disorder
Two main ways to diagnose:
Analysis of fetal cells
Amniocentesis
Chorionic villus biopsy
Imaging techniques
Ultrasonography (computerized image)
Fetoscopy (direct observation)

70. Amniocentesis Amniocentesis
Amniotic fluid is the fluid that surrounds a fetus inside the uterus
Also contains fetal cells
A sample of amniotic fluid is taken and cells are grown in a lab
Can be used to make a karyotype – takes 10 days to grow enough cells
Detects chromosome abnormalities
Can be analyzed for defective alleles
Detects other genetic disorders
Cannot be conducted until the 14th week of pregnancy

71. Amniocentesis

72. Chorionic Villus Biopsy
Chorionic villi are structures that help maximize the surface area for nutrient and gas exchange between a mother and developing fetus (they are part of the placenta)
The villi develop from fetal cells and therefore have the same chromosomes as the fetus & amniotic fluid
A sample of these cells can be taken and analyzed as in amniocentesis
Karyotyping
Tests for recessive alleles
Can be done as early as the 9th week of pregnancy

73. Ultrasonography
Uses high-frequency sound waves which bounce off of tissue
Depending on the density of tissue, waves “echo” back at different wavelengths and are used to produce a computerized image called an echogram
Used in most pregnancies to detect the position and anatomy of the fetus
Used with amniocentesis to reduce risk of injury
Can also help doctors detect abnormalities such as congenital heart defects

74. Fetoscopy A small incision is made in a pregnant woman’s abdomen
An endoscope tube is inserted through the incision
Has a camera on the end that shows an image on a monitor
Instruments can be inserted through the endoscope to perform additional procedures

75. Developing Cures for Genetic Disorders
Gene therapy
Introducing normal genes into the cells of people with defective alleles
Using viruses to inject alleles into cells
Enclosing alleles in droplets of fat, which are taken into cells by endocytosis
Currently these are still experimental procedures and have had limited success

76. Application: 1. Differentiate Autosomal Disorder and Sex Linked Disorders and give examples and characteristics