Chapter 14 The Human Genome

Human Chromosomes Our Focus this Chapter: Karyotype Sex Determination Genes and the Environment Genes and Inheritance Polygenic Dominant vs. Recessive Pedigree Charts and Punnett Squares Human Genes Inheritance Patterns Gene Inheritance: Polygenic, dominant, recessive, codominant, sex-linked, linked Chromosomal Disorders

Karyotype Autosomes: Body chromosomes (#1-22) Sex Chromosomes Male or Female? (hint: the one in your notes is different from this one)#23

Fertilization Chart Haploid (23) Diploid (46)

Sex Determination Punnett Square Probability: 50% male 50% female

Human Genes What is a gene? A segment of DNA coding for a protein (phenotype)

Genes and the Environment Influences on Gene Expression (phenotype) Nature vs. Nurture Gene expression Nutrition Exercise Stress epigenetics http://learn.genetics.utah.edu/content/epigenetics/nutrition/

Genes and Inheritance Polygenic Traits: -Multiple genes on different chromosomes affecting one trait Combination of dominant and recessive Ex: Hair color, Eye Color, Height Multiple Allele More than 2 possible alleles, in the population,for 1 genes Each individual still only has 2 alleles Ex. Blood Type IA, IB, i UP to 8 genes that control eye color: From one source http://www.sewanee.edu/chem/Chem&Art/Detail_Pages/ColorProjects_2003/Guttery/index.htm Right now there are three known gene pairs that control eye color. The bey 2 gene on chromosome 15 contains a brown and blue allele. Also on chromosome 15, the bey 1 gene is the central brown gene. On chromosome pair 19 the gey gene contains a green allele and a blue allele. A green allele is dominant over a blue allele, and a brown allele is dominant over both green and blue alleles. For the bey 2 gene if a person has a brown allele then they will have brown eyes. In the gey gene the green allele is dominant over the blue allele, but it is still recessive next to a brown allele. For example if a person has a brown allele on chromosome 15, but all the other alleles are blue or green, they will have brown eyes. A green eyed person would have a green allele on chromosome 19 and all or some other blue alleles. Blue eyes are produced only with two blue eye genes. All four alleles must be blue to produce a blue eyed person.

Genes and Inheritance Dominant vs. Recessive Incomplete Dominance Recessive alleles are masked in the presence of a dominant allele Incomplete Dominance is a form of intermediate inheritance in which one allele for a specific trait is not completely dominant over the other allele. Codominant -(blood type)

Pedigree Chart (traces family history) Figure 14-3 A Pedigree Section 14-1 A circle represents a female. A square represents a male. A horizontal line connecting a male and female represents a marriage. A vertical line and a bracket connect the parents to their children. A half-shaded circle or square indicates that a person is a carrier of the trait. A circle or square that is not shaded indicates that a person neither expresses the trait nor is a carrier of the trait. A completely shaded circle or square indicates that a person expresses the trait. Use a Punnett Square (determines probability) to illustrate the genetic probability of the first couple’s offspring. Problem Solving: p343

Blood Type Multiple Allele (A, B, O) Codominant (A and B) Dominant/Recessive (A & B are dominant over O) . any of a type of specific antigen present on the surface of red blood cells, persons having inherited such antigens being designated Rh+ (Rh positive) and persons lacking them, a much smaller group, being designated Rh− (Rh negative) blood of Rh− persons is incompatible with Rh+ blood because of antibody reaction, and an Rh− woman who bears an Rh+ baby will have formed antibodies to the fetal blood that, unless removed from her bloodstream by apheresis in a subsequent pregnancy, will be carried across the placenta and destroy red blood cells of the next Rh+ fetus, resulting in erythroblastosis in the newborn.

Blood Type in the Human Population  

Human Genes Blood Type Disorders Gene Chromosomal Autosomal Sex-linked Recessive Dominant Codominant Sex-linked Chromosomal

Autosomal Recessive Both copies of the gene must be the recessive allele Represented by a lower case letter Albinism – Phenylketonuria – Tay Sachs – Galactosemia – Cystic Fibrosis – Chart p345

Autosomal Recessive Albinism Genotype: aa Expression: Missing Melanin (pigment) Lack of color in skin, hair and eyes Vision impairment Treatment: Glasses, eye surgery

Autosomal Recessive Phenylketonuria (PKU) Genotype: (chromosome 12) pp Expression: Missing phenylalanine hydroxylase Inability to process phenylalanine Abnormal pigment Mental retardation Treatment Specialized diet low in phenylalanine Phenylalanine occurs in significant amounts in milk, eggs, and other common foods. The artificial sweetener NutraSweet (aspartame) also contains phenylalanine. Any products containing aspartame should be avoided. A special infant formula called Lofenalac is made for infants with PKU. It can be used throughout life as a protein source that is extremely low in phenylalanine and balanced for the remaining essential amino acids. Phenylketonuria (PKU) is inherited, which means it is passed down through families. Both parents must pass on the defective gene in order for a baby to have the condition. This is called an autosomal recessive trait. Babies with PKU are missing an enzyme called phenylalanine hydroxylase, which is needed to break down an essential amino acid called phenylalanine. The substance is found in foods that contain protein. Without the enzyme, levels of phenylalanine and two closely-related substances build up in the body. These substances are harmful to the central nervous system and cause brain damage. Taking supplements such as fish oil to replace the long chain fatty acids missing from a standard phenylalanine-free diet may help improve neurologic development, including fine motor coordination. Other specific supplements, such as iron or carnitine, may be needed.

Autosomal Recessive Tay Sachs Genotype: (chromosome 15) tt Expression: Lack enzyme hexosaminidase A Lipid accumulation in brain, blindness, mental deficiency, death Treatment: None Genetic testing available

Autosomal Recessive Cystic Fibrosis Genotype: (chromosome 12) cc Expression: Deletion of 3 bases = loss of phenylalanine in gene Abnormal chloride channels cannot be transported to membrane No chloride channels causes airways to become clogged with thick mucous Treatment Drug therapies and lung therapies extend lives

Autosomal Dominant Only one copy of the genes is necessary to exhibit the trait Represented by a capital letter Achondroplasia Huntington’s Disease Hypercholesterolemia

Autosomal Dominant Huntington Disease Genotype: (chromosome 4) Hh Expression: Extensive repetition of CAG on DNA Adult-onset Neurological Symptoms Include: Disorientation or confusion, Loss of judgment, Loss of memory, Speech changes Death (usually by 50) Treatment Medications used to slow symptoms Guthrie’s wife founded the Huntington’s Disease Society of America in 1977 which funds and conducts research on HD Singer/Songwriter Woody Guthrie “This Land is Your Land”

Autosomal Dominant Achondroplasia (dwarfism) Genotype: (chromosome 4) Aa Expression: Problems with bone ossification of long bones Effect growth Average head and torso with shortened arms and legs Fun Fact 80% of Achondroplasia cases are new mutations primarily from men >35     Shown on the right are seven pseudoachondroplasic members of the Ovitz family, a family of Romanian Jews who toured eastern Europe as a musical troupe before World War II (their taller siblings working backstage), survived imprisonment at Auschwitz, and finally emigrated to Israel. They were photographed on arrival in Haifa in 1949. Their father was (apparently) of ordinary height and was twice married, both times to women of ordinary height. With his first wife, he had two affected daughters [possibly the two older women in flowered dresses], and with his second five affected children (three girls and two boys) shown here, as well as three children of ordinary height. This suggests the father had a germline mutation p P, in which case the expected ratio from Pp x pp 50% "P" : 50% "p", as compared with the observed ratio of 7 affected : 3 unaffected children. Note that this departure from expectation is the same ratio of girls to boys. [Homework: test the ratios by chi-square and 2x2 contingency tests]. The sons are reported to have had taller children (Pp x pp 50% "pp"); the daughters were unable to bear children because of their narrow pelvises

Codominant 2 alleles can be expressed at the same time Sickle Cell Anemia HA – normal allele HS - sickle cell HA HA , HA HS, HS HS

Sickle Cell Anemia HA HA HA HS HS HS Normal Sickle Cell Trait Sickle Cell Disease Normal Hemoglobin Both normal and abnormal hemoglobin Abnormal hemoglobin Normal rbc shape Normal and sickle shape Sickle shaped rbc

Distribution of Sickle Cell Anemia vs. Malaria 10% of African Americans and 40% of populations in Africa and Asia carry the gene for Sickle Cell Anemia

From gene to molecule DNA normal hemoglobin CAC GTG GAC TGA GGA CTC CTC mRNA Amino acid sequence (p303) DNA Sickle Cell Anemia CAC GTG GAC TGA GGA CAC CTC amino acid GUG CAC CUG ACU CCU GAG GAG Val – His – Leu – Thr – Pro – Glu – Glu… 1 2 3 4 5 6 7 …146 GUG CAC CUG ACU CCU GUG GAG Val – His – Leu – Thr – Pro–VAL – Glu… 1 2 3 4 5 6 7 …146

Sex-Linked Genes Genes that are found on the X (or Y) chromosome and are linked to a person’s gender. Recessive type seems to disappear only to reappear later. Males have a higher chance of having sex-linked disorders. They only need one copy of the gene in order to express it. Examples: colorblindness, hemophilia, Duchenne Musclar Dystropy

Sex-linked Recessive Red-Green Colorblindness Normal Vision would be able to see all #s XCXC, XCXc XCY A colorblind person could see 25 and 56 XcXc XcY

Sex-linked Recessive Red-Green Colorblindness

Sex-linked Recessive Hemophilia Genotype: XhXh, XhY carrier: XHXh Expression: Lack of clotting factors for blood Bleeder’s disease Can die if bleeding is left untreated Treatment: Clotting factor replacement Gene therapy* (what is gene therapy?) The transplantation of normal genes into cells in place of missing or defective ones in order to correct genetic disorders. Gene therapy works by a normal gene is placed where a missing or defective gene is to try and fix the problem. Gene therapy is used in Hemophilia. 

Royal Family and Hemophilia

Sex-linked Recessive Duchenne Muscular Dystrophy Genotype: XmXm, XmY carrier: XMXm Expression: Defective protein in muscle (dystrophin) Fatigue Learning difficulties (IQ can be below 75) Muscle weakness Eventually, inability to walk and breathe Death by 25 Treatment: Steroid drugs and supplements Working on gene therapy

X-inactivation Females have 2 copies of X One is randomly turned off early in development Different cells have different Xs active

Chromosomal Disorders Rather than 1 gene effecting one protein an entire chromosome is deleted or added. Cause: Non-disjunction of chromosomes (autosomes or sex chromosomes) during meiosis Examples: Down Syndrome, Turner’s Klinefelter’s

Homologous chromosomes fail to separate Nondisjunction Section 14-2 Homologous chromosomes fail to separate Meiosis I: Nondisjunction Meiosis II Go to Section:

Homologous chromosomes fail to separate Nondisjunction Section 14-2 Homologous chromosomes fail to separate Meiosis I: Nondisjunction Meiosis II Go to Section:

Homologous chromosomes fail to separate Nondisjunction Section 14-2 Homologous chromosomes fail to separate Meiosis I: Nondisjunction Meiosis II Go to Section:

Chromosomal Disorder Down Syndrome Genotype: (autosomal) 47 XX +21 Expression: Non-disjunction of chromosome 21 Mental retardation, growth failure, intestinal and heart problems, leukemia, early onset Alzheimer’s Treatment: No specific treatment

Incidence of Down’s Syndrome and mother’s age

Chromosomal Disorders Non disjunction of sex chromosomes leads to extra of loss of an X or Y chromosome

Chromosomal Disorders Turner’s Syndrome Genotype: (sex chromosome) 45 XO Expression: Female Sterile Sex organs do not fully develop during puberty Treatment Growth hormone treatment, estrogen treatment

Chromosomal Disorders Klinefelter’s Syndrome Genotype: (sex chromosome) 48 XXXY Expression: Male Sterile Breast growth Language problems Lower energy Treatment Testosterone replacement, speech therapy, breast reduction, physical therapy