THE HUMAN GENOME

1. THE HUMAN GENOME • The children in this family have some traits that are similar to their mother’s and some that are similar to their father’s

2. Human Heredity • Of all the living things that inhabit this remarkable world, there is one in particular that has always drawn our interest, one that has always made us wonder, one that will always fire our imagination • That creature is, of course, ourselves, Homo sapiens

3. Human Heredity • Scientists once knew much less about humans than about other organisms • Until very recently, human genetics lagged far behind the genetics of “model” organisms such as fruit flies and mice • That, however, has changed • Scientists are now on the verge of understanding human genetics at least as well as they understand that of some other organisms • From that understanding will come a new responsibility to use that information wisely

4. Human Chromosomes • What makes us human? • Biologists can begin to answer that question by taking a look under the microscope to see what is inside a human cell • To analyze chromosomes, cell biologists photograph cells in mitosis, when the chromosomes are fully condensed and easy to see • The biologists then cut out the chromosomes from the photographs and group them together in pairs • A picture of chromosomes arranged in this way is known as a karyotype

5. KAROTYPE • Photograph of the chromosomes of a cell, arranged in order from the largest to the smallest

6. KAROTYPE OF NORMAL CELL

7. Human Chromosomes • The chromosomes shown are from a typical human body cell • The number of chromosomes—46—helps identify this karyotype as human • This karyotype is the result of a haploid sperm, carrying just 23 chromosomes, fertilizing a haploid egg, also with 23 chromosomes • The diploid zygote, or fertilized egg, contained the full complement of 46 chromosomes

8. DOWN’S SYNDROME • Nondisjunction of the 21st chromosome • Extra copy of the 21st chromosome • Results in abnormal eyelids, noses with low bridges, large tongues, and hands that are short and broad • Usually short in stature • Often mentally retarded • Many deformed heart

9. Karyotype  • These human chromosomes have been cut out of a photograph and arranged to form a karyotype.

10. KAROTYPE OF DOWN’S SYNDROME

11. Human Chromosomes • Two of those 46 chromosomes are known as sex chromosomes, because they determine an individual's sex • Females have two copies of a large X chromosome(XX) • Males have one X and one small Y chromosome(XY) • To distinguish them from the sex chromosomes, the remaining 44 chromosomes are known as autosomal chromosomes, or autosomes • To quickly summarize the total number of chromosomes present in a human cell, both autosomes and sex chromosomes, biologists write 46,XX for females and 46,XY for males

12. Human Chromosomes • As you can see in the figure, males and females are born in a roughly 50 : 50 ratio because of the way in which sex chromosomes segregate during meiosis • All human egg cells carry a single X chromosome (23,X) • However, half of all sperm cells carry an X chromosome (23,X) and half carry a Y chromosome (23,Y) • This ensures that just about half of the zygotes will be 46,XX and half will be 46,XY • The human male determines the sex of the next generation

13. Human Chromosomes

14. Human Chromosomes • Segregation of Sex Chromosomes: • In humans, egg cells contain a single X chromosome • Sperm cells contain either one X chromosome or one Y chromosome • In a population, approximately half of the zygotes are XX (female) and half are XY (male)

15. Human Traits • Human genes are inherited according to the same principles that Gregor Mendel discovered in his work with garden peas • However, in order to apply Mendelian genetics to humans, biologists must identify an inherited trait controlled by a single gene • First, they must establish that the trait is actually inherited and not the result of environmental influences • Then, they have to study how the trait is passed from one generation to the next

16. GENETICS • Sex-Linked Traits: • Examples: • Hemophilia: disease in which there is the inability to form a blood clot • Recessive trait • Genes for the proteins necessary for blood clotting are located on the X chromosome • A pedigree (diagram of relationships in the family genetic line) can be used to show the history of a disease in a family • Circle represents a female • Square represents a male • Filled-in symbols represents a person who is homozygous recessive for the alleles • Half-filled symbols represent carriers

17. Pedigree Charts  • A pedigree chart, which shows the relationships within a family, can be used to help with this task • The pedigree in the figure at right shows how an interesting human trait, a white lock of hair just above the forehead, is transmitted through three generations of a family • The allele for the white forelock trait is dominant • At the top of the chart is a grandfather who had the white forelock trait • Two of his three children inherited the trait, although one child did not • Three grandchildren have the trait, and two do not

18. Pedigree Charts 

19. Pedigree Charts  • Genetic counselors analyze pedigree charts to infer the genotypes of family members • For example, since the white forelock trait is dominant, all the family members that lack the trait must have homozygous recessive alleles • Since one of the grandfather's children lacks the white forelock trait, the grandfather must be heterozygous for the trait • Colorblindness and hemophilia can be traced the same way through generations of a family

20. PEDIGREE

21. PEDIGREE

22. Genes and the Environment  • Unfortunately for folks who would like to settle burning issues, like which side of the family is responsible for your good looks, some of the most obvious human traits are almost impossible to associate with single genes • There are two reasons for this: • First, things you might think of as single traits, such as the shape of your eyes or ears, are actually polygenic, meaning they are controlled by many genes • Second, many of your personal traits are only partly governed by genetics

23. Genes and the Environment • Remember that the phenotype of an organism is only partly determined by its genotype • Many traits are strongly influenced by environmental, or nongenetic, factors, including nutrition and exercise • For example, even though a person's maximum possible height is largely determined by genetic factors, nutritional improvements in the United States and Europe have increased the average height of these populations about 10 centimeters over their average height in the 1800s

24. Genes and the Environment  • Although it is important to consider the influence of the environment on the expression of some genes, it must be understood that environmental effects on gene expression are not inherited; genes are • Genes may be denied a proper environment in which to reach full expression in one generation • However, these same genes can, in a proper environment, achieve full potential in a later generation

25. Human Genes • The human genome—our complete set of genetic information—includes tens of thousands of genes • The DNA sequences on these genes carry information for specifying many characteristics, from the color of your eyes to the detailed structures of proteins within your cells • The exploration of the human genome has been a major scientific undertaking • By 2000, the DNA sequence of the human genome was almost complete

26. Human Genes • Studying the genetics of our species has not been easy • Until recently, the identification of a human gene took years of scientific work • Humans have long generation times and a complex life cycle, and they produce, at least compared with peas and fruit flies, very few offspring • Still, in a few cases, biologists were able to identify genes that directly control a single human trait • Some of the very first human genes to be identified were those that control blood type

27. Blood Group Genes  • Human blood comes in a variety of genetically determined blood groups • Knowing a person's blood group is critical because using the wrong type of blood for a transfusion during a medical procedure can be fatal • A number of genes are responsible for human blood groups, but the best known are the ABO blood groups and the Rh blood groups

28. Blood Group Genes  • The Rh blood group is determined by a single gene with two alleles—positive and negative • Rh stands for “rhesus monkey,” the animal in which this factor was discovered • The positive (Rh+) allele is dominant, so persons who are Rh+/Rh+ or Rh+/Rh− are said to be Rh-positive • Individuals with two Rh− alleles are Rh-negative

29. Blood Group Genes  • The ABO blood group is more complicated • There are three alleles for this gene, IA, IB, and i • Alleles IA and IB are codominant • These alleles produce molecules known as antigens on the surface of red blood cells • Individuals with alleles IA and IB produce both A and B antigens, making them blood type AB • The i allele is recessive • Individuals with alleles IAIA or IAi produce only the A antigen, making them blood type A • Those with IBIB or IBi alleles are type B • Those who are homozygous for the i allele (ii) produce no antigen, and are said to have blood type O

30. MULTIPLE ALLELES

31. MULTIPLE ALLELES

32. Blood Group Genes 

33. Blood Group Genes  • Blood Groups: • This table shows the relationship between genotype and phenotype for the ABO blood group • It also shows which blood types can safely be transfused into people with other blood types

34. Blood Group Genes • When a medical worker refers to blood groups, he or she usually mentions both groups at the same time • For example, if a patient has AB-negative blood, it means the individual has IA and IB alleles from the ABO gene and two Rh− alleles from the Rh gene

35. MULTIPLE ALLELES

36. Recessive Alleles  • Many human genes have become known through the study of genetic disorders • The table lists some common genetic disorders • In most cases, the presence of a normal, functioning gene is revealed only when an abnormal or nonfunctioning allele affects the phenotype

37. Recessive Alleles 

38. Recessive Alleles  • One of the first genetic disorders to be understood this way was phenylketonuria, or PKU • People with PKU lack the enzyme that is needed to break down phenylalanine • Phenylalanine is an amino acid found in milk and many other foods • If a newborn has PKU, phenylalanine may build up in the tissues during the child's first years of life and cause severe mental retardation • Fortunately, newborns can be tested for PKU and then placed on a low-phenylalanine diet that prevents most of the effects of PKU • PKU is caused by an autosomal recessive allele carried on chromosome 12

39. Recessive Alleles  • Many other disorders are also caused by autosomal recessive alleles • One is Tay-Sachs disease, which is caused by an allele found mostly in Jewish families of central and eastern European ancestry • Tay-Sachs disease results in nervous system breakdown and death in the first few years of life • Although there is no treatment for Tay-Sachs disease, there is a test for the allele • By taking this test, prospective parents can learn whether they are at risk of having a child with the disorder

40. Dominant Alleles  • Not all genetic disorders are caused by recessive alleles • You may recall that the effects of a dominant allele are expressed even when the recessive allele is present • Therefore, if you have a dominant allele for a genetic disorder, it will be expressed • Two examples of genetic disorders caused by autosomal dominant alleles are a form of dwarfism known as achondroplasia and a nervous system disorder known as Huntington's disease • Huntington's disease causes a progressive loss of muscle control and mental function until death occurs • People who have this disease generally show no symptoms until they are in their thirties or older, when the gradual damage to the nervous system begins

41. HUNTINGTON’S DISEASE

42. Codominant Alleles  • Sickle cell disease, a serious disorder found in about 1 out of 500 African Americans, is caused by a codominant allele

43. From Gene to Molecule • How do the actual DNA sequences in genes affect phenotype so profoundly? • What is the link between the DNA bases in the allele for a genetic disorder and the disorder itself? • For many genetic disorders, scientists are still working to find the answer • But for two disorders, the connection is understood very well indeed • In both cystic fibrosis and sickle cell disease, a small change in the DNA of a single gene affects the structure of a protein, causing a serious genetic disorder

44. Cystic Fibrosis  • Cystic fibrosis, or CF, is a common genetic disease • Cystic fibrosis is most common among people whose ancestors came from Northern Europe • The disease is caused by a recessive allele on chromosome 7 • Children with cystic fibrosis have serious digestive problems • In addition, they produce a thick, heavy mucus that clogs their lungs and breathing passageways

45. Cystic Fibrosis 

46. Cystic Fibrosis  • Cystic fibrosis involves a very small genetic change • The figure illustrates how information carried in a chromosome's DNA specifies the trait of cystic fibrosis • Most cases of cystic fibrosis are caused by the deletion of 3 bases in the middle of a sequence for a protein • This protein normally allows chloride ions (Cl−) to pass across biological membranes • The deletion of these 3 bases removes just one amino acid from this large protein, causing it to fold improperly

47. Cystic Fibrosis • Because of this, the cells do not transport the protein to the cell membrane, and the misfolded protein is destroyed • Unable to transport chloride ions, tissues throughout the body malfunction • People with one normal copy of the allele are unaffected, because they can produce enough of the chloride channel protein to allow their tissues to function properly

48. Sickle Cell Disease  • Sickle cell disease is a common genetic disorder found in African Americans • Sickle cell disease is characterized by the bent and twisted shape of the red blood cells • These sickle-shaped red blood cells are more rigid than normal cells and tend to get stuck in the capillaries, the narrowest blood vessels in the body • As a result, blood stops moving through these vessels, damaging cells, tissues, and organs • Sickle cell disease produces physical weakness and damage to the brain, heart, and spleen • In some cases, it may be fatal

49. Sickle Cell Disease 

50. Sickle Cell Disease  • Sickle Cell Disease: • These red blood cells contain the abnormal hemoglobin characteristic of sickle cell disease.