Unit 11Unit 11Human GeneticsHuman Genetics

I. How can you study human heredity?I. How can you study human heredity?A. ProblemsA. Problems1.1. You cannot ethically conduct a You cannot ethically conduct a testcrosstestcross or other breeding or other breeding experiments in humans. A testcross experiments in humans. A testcross is a method of is a method of determining thedetermining the unknown genotypeunknown genotype of a parent with a of a parent with a

dominant phenotype. The experimenter dominant phenotype. The experimenter breeds the organism of unknown breeds the organism of unknown genotype genotype with a with a homozygous recessivehomozygous recessive organism and organism and examines the resulting examines the resulting offspring.offspring.

Example: A guinea pig with brown Example: A guinea pig with brown fur(BB or Bb) is crossed with a white fur(BB or Bb) is crossed with a white guinea guinea pig (bb). If any offspring are pig (bb). If any offspring are white, the white, the unknown genotype must be Bb.unknown genotype must be Bb.

2.2. Humans, thankfully, have a Humans, thankfully, have a long life long life spanspan. Unfortunately, this makes us . Unfortunately, this makes us bad candidates for active multi-bad candidates for active multi-generational studies. It may take generational studies. It may take decades to produce several decades to produce several generationsgenerations within one family, making within one family, making it difficult to study a particular trait in it difficult to study a particular trait in that family.that family.

3.3. By comparison, humans have a By comparison, humans have a small small number of offspringnumber of offspring and a and a long long gestational periodgestational period, providing fewer , providing fewer experimental subjects and less experimental subjects and less statistical certainty.statistical certainty.

B.B. Techniques to Study Human HeredityTechniques to Study Human Heredity

1. 1. Population samplingPopulation sampling determines how determines how often a trait appears in a often a trait appears in a small, randomly small, randomly selected groupselected group. This percentage is then . This percentage is then applied to the entire populationapplied to the entire population to predict to predict the number of individuals with that trait.the number of individuals with that trait.

2. 2. PedigreesPedigrees graphically record the graphically record the inheritance of a single trait over several inheritance of a single trait over several generationsgenerations. Typically, the occurrence of . Typically, the occurrence of the trait is determined based on the trait is determined based on family/historical documents, interviews, family/historical documents, interviews, photographs, and medical records. photographs, and medical records.

a.a. Specific shapes are used to represent Specific shapes are used to represent individuals in a pedigree:individuals in a pedigree:

IndividualIndividual With TraitWith Trait Without TraitWithout Trait

FemaleFemale

MaleMale

b.b. Connecting lines are used to indicate Connecting lines are used to indicate relationships among individuals within relationships among individuals within the family.the family.

P1P1

parentalparental

F1F1

first filialfirst filial

F2F2

Second filialSecond filial

c. Pedigrees c. Pedigrees demonstrate the pattern of demonstrate the pattern of inheritanceinheritance (dominant/recessive, sex-linked) (dominant/recessive, sex-linked) of the single trait.of the single trait.

d. Pedigrees can be interpreted to d. Pedigrees can be interpreted to determine the determine the presence of carrierspresence of carriers (individuals who do not express the trait but (individuals who do not express the trait but may pass the gene on to offspring).may pass the gene on to offspring).

Example: The two parents (P1 generation) Example: The two parents (P1 generation) must have been carriers (Bb) for a recessive must have been carriers (Bb) for a recessive trait. Neither showed the trait, but they had trait. Neither showed the trait, but they had a child with the trait (bb).a child with the trait (bb).

Review Questions:Review Questions:1. 1. List 3 reasons that it is difficult to List 3 reasons that it is difficult to

study genetics in humans.study genetics in humans.can not conduct breeding experiments, long life span and too few can not conduct breeding experiments, long life span and too few offspringoffspring

2.2. What is a testcross?What is a testcross? A testcross is a method of determining the unknown genotype of a A testcross is a method of determining the unknown genotype of a

parent with a dominant phenotype.parent with a dominant phenotype. 3.3. What do pedigrees tell us about the What do pedigrees tell us about the

inheritance of a trait in a family?inheritance of a trait in a family? Pedigrees demonstrate the pattern of inheritance Pedigrees demonstrate the pattern of inheritance (dominant/recessive, sex-linked) of the single trait.(dominant/recessive, sex-linked) of the single trait.

Practice PedigreePractice PedigreeType O blood is recessive to Type A and B Type O blood is recessive to Type A and B blood. Tom had type B blood and married blood. Tom had type B blood and married Shana who had type A blood. Together, Shana who had type A blood. Together, they had 2 children: Cherith (Type O) and they had 2 children: Cherith (Type O) and Bryan (Type AB). Bryan married Ali (Type Bryan (Type AB). Bryan married Ali (Type O) and they had 2 children: Christian O) and they had 2 children: Christian (Type A) and Jon (who could not donate (Type A) and Jon (who could not donate blood to Christian). Ali had an affair with blood to Christian). Ali had an affair with Trent, who was homozygous for blood type Trent, who was homozygous for blood type A. Ali and Trent had a child with Type A A. Ali and Trent had a child with Type A blood.blood.

II.II. How do you get a genetic disease?How do you get a genetic disease?A. A. Gene disorders are inherited as a Gene disorders are inherited as a single gene on a chromosomesingle gene on a chromosome. Most . Most gene disorders are gene disorders are recessiverecessive. Thus, in . Thus, in order to express the disorder, the order to express the disorder, the individual must be homozygous individual must be homozygous recessive. Science hypothesizes that recessive. Science hypothesizes that gene disorders arose from mutationsgene disorders arose from mutations that disabled specific proteins.that disabled specific proteins.

1. 1. AutosomalAutosomal genetic diseases occur genetic diseases occur when the gene defect is on one of the when the gene defect is on one of the first 22 pairsfirst 22 pairs of chromosomes (called of chromosomes (called the autosomal chromosomes).the autosomal chromosomes).

a.a. Huntington’s diseaseHuntington’s disease is inherited as an is inherited as an autosomal dominant gene. Huntington’s autosomal dominant gene. Huntington’s disease disease breaks down certain areas of the breaks down certain areas of the brainbrain. In addition to being dominant, . In addition to being dominant, Huntington’s is also unique because Huntington’s is also unique because symptoms begin appearing in the person’s symptoms begin appearing in the person’s late forties.late forties.

b.b. Sickle-cell anemiaSickle-cell anemia is inherited as a is inherited as a codominantcodominant autosomal gene. Sickle-cell autosomal gene. Sickle-cell anemia leads to anemia leads to misshapen red blood cellsmisshapen red blood cells which lead to poor circulation and pain. which lead to poor circulation and pain. Sickle cell is unique because Sickle cell is unique because heterozygous heterozygous individuals are not afflicted by sickle cell individuals are not afflicted by sickle cell AND are able to resist malariaAND are able to resist malaria (which is (which is handy in certain areas of the world). handy in certain areas of the world). Currently, sickle cell is primarily in African Currently, sickle cell is primarily in African populations.populations.

c.c. Cystic fibrosisCystic fibrosis is inherited as a is inherited as a recessiverecessive autosomal gene. Cystic fibrosis leads to autosomal gene. Cystic fibrosis leads to increased mucus productionincreased mucus production in the lungs in the lungs and digestive tract, which may be fatal. and digestive tract, which may be fatal. Currently, this disease is primarily in Currently, this disease is primarily in Caucasian populations. Caucasian populations.

d.d. Tay-Sach’sTay-Sach’s is inherited as a is inherited as a recessiverecessive autosomal gene. Tay-Sach’s autosomal gene. Tay-Sach’s degeneratesdegenerates (breaks down) the (breaks down) the central nervous systemcentral nervous system leading to premature death. Currently, Tay-leading to premature death. Currently, Tay-Sach’s is primarily in Jewish and Sach’s is primarily in Jewish and Pennsylvania Dutch populations.Pennsylvania Dutch populations.

Alyssa Gold

                                                                 

May 30, 1997 - March 17, 2001

e.e. Phenylketonuria (Phenylketonuria (PKUPKU) is inherited as ) is inherited as recessiverecessive autosomal gene. PKU leads to the autosomal gene. PKU leads to the inability to break down the amino acid inability to break down the amino acid phenylalaninephenylalanine when ingested. The when ingested. The phenylalanine builds up in the brain and phenylalanine builds up in the brain and leads to decreased mental function. PKU is leads to decreased mental function. PKU is unique because, if detected early, it unique because, if detected early, it can be can be entirely controlled by dietentirely controlled by diet. Individuals can . Individuals can simply not consume products containing simply not consume products containing phenylalanine (such as milk and diet sodas). phenylalanine (such as milk and diet sodas). However, any damage done before However, any damage done before detection is irreversible. In hospitals, detection is irreversible. In hospitals, children are tested at birth.children are tested at birth.

2.2. Sex-linked genetic diseases occur Sex-linked genetic diseases occur when the gene defect is on the last when the gene defect is on the last pair (23rd) of chromosomespair (23rd) of chromosomes (called the (called the sex chromosomes). Because males sex chromosomes). Because males inherit only a single X chromosome inherit only a single X chromosome (they are XY) and the X carries the (they are XY) and the X carries the majority of sex-linked genes, majority of sex-linked genes, males males are MORE LIKELY to express sex-linked are MORE LIKELY to express sex-linked disorders and cannot be carriers of disorders and cannot be carriers of these traitsthese traits. .

a.a. HemophiliaHemophilia is inherited as a is inherited as a recessive recessive sex-linked genesex-linked gene. Hemophilia leads to . Hemophilia leads to low production of blood clotting low production of blood clotting factorsfactors which leads to excessive which leads to excessive bruising and bleeding. bruising and bleeding.

b.b. Red-green color blindnessRed-green color blindness in inherited in inherited

as a as a recessive sex-linked generecessive sex-linked gene. People . People with red-green color blindness are with red-green color blindness are unable to distinguish red from green unable to distinguish red from green colorscolors (both colors often appear a (both colors often appear a muddy brown).muddy brown).

B.B. Chromosomal disorders are inherited due to Chromosomal disorders are inherited due to problems with an entire chromosomeproblems with an entire chromosome (which (which may contain hundreds of genes!) Thus, an may contain hundreds of genes!) Thus, an individual with even one chromosomal individual with even one chromosomal defect will most likely express the disorder. defect will most likely express the disorder. Science hypothesizes that Science hypothesizes that chromosomal chromosomal disorders arise from mistakes in meiosisdisorders arise from mistakes in meiosis during gamete formation. For example, a during gamete formation. For example, a sperm cell may receive 22 instead of 23 sperm cell may receive 22 instead of 23 chromosomes. This chromosomes. This incorrect distribution of incorrect distribution of chromosomes is called nondisjunction. chromosomes is called nondisjunction. Nondisjunction may lead to aneuploidy - an Nondisjunction may lead to aneuploidy - an incorrect number of chromosomes in a incorrect number of chromosomes in a fertilized zygote.fertilized zygote.

1.1. An An autosomal chromosome autosomal chromosome aneuoploidyaneuoploidy refers to having one extra refers to having one extra autosome. For example, autosome. For example, Trisomy 21Trisomy 21 (three #21 chromosomes), leads to (three #21 chromosomes), leads to Down’s SyndromeDown’s Syndrome. Characteristics of . Characteristics of Down’s Syndrome include Down’s Syndrome include some level some level of mental retardation, heart defects, of mental retardation, heart defects, flat facial features, and an enlarged flat facial features, and an enlarged tonguetongue..

2.2. A A sex chromosome aneuploidysex chromosome aneuploidy refers to refers to having one extra or one too few sex having one extra or one too few sex chromosomes. chromosomes.

a.a. Turner’sTurner’s Syndrome is the result of inheriting Syndrome is the result of inheriting a single X chromosome (a single X chromosome (genotype XOgenotype XO). ). These individuals are These individuals are female but lack female but lack secondary sex characteristics, are infertile, secondary sex characteristics, are infertile, and have some lack of mental functionand have some lack of mental function..

b.b. Klinefelter’s Klinefelter’s Syndrome is the result of Syndrome is the result of inheriting an extra X chromosome in males inheriting an extra X chromosome in males ((genotype XXYgenotype XXY). These individuals are ). These individuals are male male but lack secondary sex characteristics, are but lack secondary sex characteristics, are infertile, and have some lack of mental infertile, and have some lack of mental functionfunction..

Review Questions:Review Questions:1. What is the difference between a gene 1. What is the difference between a gene

disorder and a chromosomal disorder?disorder and a chromosomal disorder?A gene disorder is caused by a incorrect single gene on a A gene disorder is caused by a incorrect single gene on a chromosome. A chromosomal disorder is caused by the chromosome. A chromosomal disorder is caused by the inheritance of too many or not enough total chromosomes.inheritance of too many or not enough total chromosomes.

2. What is the difference between an 2. What is the difference between an autosomal disorder and a sex-linked autosomal disorder and a sex-linked disorder?disorder?An autosomal disorder is carried on the first 22 pairs of An autosomal disorder is carried on the first 22 pairs of chromosomes. A sex linked disorder is carried on the X chromosomes. A sex linked disorder is carried on the X chromosome.chromosome.

3. Why is hemophilia considered a sex-linked 3. Why is hemophilia considered a sex-linked disease?disease?It is carried on the X chromosomeIt is carried on the X chromosome

4. What is an aneuploidy?4. What is an aneuploidy? aneuoploidy refers to having one extra chromosomeaneuoploidy refers to having one extra chromosome

III.III. Can we tell if a baby has a genetic disease?Can we tell if a baby has a genetic disease?

A.A. A A genetic counselorgenetic counselor can help prospective can help prospective parents parents determine the likelihood of passing determine the likelihood of passing some harmful genetic traits to their some harmful genetic traits to their offspringoffspring and may suggest further testing and may suggest further testing procedures. Counselors may also procedures. Counselors may also interpret interpret diagnostic proceduresdiagnostic procedures done by the doctor done by the doctor for parents.for parents.

1. 1. Sonograms use sound waves to Sonograms use sound waves to produce an image of the developing fetusproduce an image of the developing fetus. . This may be used to detect This may be used to detect physical physical abnormalitiesabnormalities (such as cleft palate). (such as cleft palate).

2.2. Blood testsBlood tests of the pregnant mother may of the pregnant mother may screen for certainscreen for certain proteins proteins to assess the risk to assess the risk level of certain genetic disorders (such as level of certain genetic disorders (such as Down’s Syndrome).Down’s Syndrome).

3.3. Amniocentesis Amniocentesis removes amniotic fluid removes amniotic fluid containing fetal cells. The cells are then containing fetal cells. The cells are then cultured until mitosis occurs and the cultured until mitosis occurs and the chromosomes are visible. A chromosomes are visible. A karyotypekaryotype (a (a picture of thepicture of the chromosomes chromosomes) is made using ) is made using the visible chromosomes. The karyotype the visible chromosomes. The karyotype allows doctors to detectallows doctors to detect chromosomal chromosomal abnormalities abnormalities but does NOT detectbut does NOT detect gene gene abnormalitiesabnormalities..

4.4. Chorionic villi samplingChorionic villi sampling ( (CVSCVS) removes ) removes actual tissue from theactual tissue from the placenta placenta (which (which is composed on embryonic cells) in is composed on embryonic cells) in order to order to create a karyotypecreate a karyotype. This may . This may be done earlier in the pregnancy, but be done earlier in the pregnancy, but is far more invasive and thus riskier.is far more invasive and thus riskier.

B.B. The Human Genome ProjectThe Human Genome Project has has allowed science to develop certain allowed science to develop certain genetic markers. A genetic markers. A genetic marker genetic marker detects the presence of certaindetects the presence of certain gene gene variations variations on the chromosomes. on the chromosomes. These genes may either be a direct These genes may either be a direct cause of a disorder or may simply cause of a disorder or may simply indicate a predisposition for a trait. indicate a predisposition for a trait. Doctors or genetic counselors may use Doctors or genetic counselors may use genetic markers to screen parents and genetic markers to screen parents and determine if the parents may be determine if the parents may be carriers forcarriers for genetic disorders genetic disorders..

Review Questions:Review Questions:1. What is the role of a genetic counselor?1. What is the role of a genetic counselor?

A genetic counselor can help prospective parents determine A genetic counselor can help prospective parents determine the likelihood of passing some harmful genetic traits to their the likelihood of passing some harmful genetic traits to their offspring and may suggest further testing procedures.offspring and may suggest further testing procedures.

2. Name 4 pre-natal tests that may detect 2. Name 4 pre-natal tests that may detect genetic disorders.genetic disorders.Sonogram, Blood Tests, Amniocentesis, CVSSonogram, Blood Tests, Amniocentesis, CVS

3. What is a karyotype?3. What is a karyotype? A karyotype (a picture of the chromosomes) is made using A karyotype (a picture of the chromosomes) is made using the visible chromosomes.the visible chromosomes.

4. How are genetic markers used?4. How are genetic markers used? A genetic marker detects the presence of certain A genetic marker detects the presence of certain gene variations on the chromosomes.gene variations on the chromosomes.

IV.IV. Can you prevent and/or treat genetic Can you prevent and/or treat genetic disorders?disorders?A. Currently, there is no “cure” for genetic A. Currently, there is no “cure” for genetic disorders because the disorder stems from disorders because the disorder stems from your DNA. However, the your DNA. However, the symptoms of symptoms of genetic disorders can be treatedgenetic disorders can be treated and and experimental trials for replacing defective experimental trials for replacing defective genes are underway.genes are underway.

1. 1. Pain medicationPain medication may be used to may be used to

manage the pain associated with certain manage the pain associated with certain genetic disorders, such as sickle-cell genetic disorders, such as sickle-cell anemia. Other medications may help limit anemia. Other medications may help limit the progression of a disorder once detectedthe progression of a disorder once detected

2.2. Occupational therapyOccupational therapy and special and special educational interventions for educational interventions for individuals with Down’s Syndrome are individuals with Down’s Syndrome are used. used. Physical therapyPhysical therapy is often used is often used for patients with cystic fibrosis to help for patients with cystic fibrosis to help loosen the mucus.loosen the mucus.

3.3. Patients with sickle-cell anemia or Patients with sickle-cell anemia or hemophilia may require hemophilia may require blood blood transfusionstransfusions or possible bone marrow or possible bone marrow transplants.transplants.

4.4. Gene therapiesGene therapies are being developed are being developed using information from the Human using information from the Human Genome Project. These therapies seek Genome Project. These therapies seek to use engineered cell invaders (such to use engineered cell invaders (such as a virus) in order to actually replace as a virus) in order to actually replace the defective gene in target cells with the defective gene in target cells with a functioning gene. a functioning gene.

B.B. Environmental factors may play a large role Environmental factors may play a large role in the expression or progression of certain in the expression or progression of certain genetic problemsgenetic problems. Environmental factors . Environmental factors that interact with genes can be controlled to that interact with genes can be controlled to help prevent the eventual expression of help prevent the eventual expression of known genetic predispositions.known genetic predispositions.

1. 1. Appropriate diet can stop the Appropriate diet can stop the progression of PKUprogression of PKU. Diet may also . Diet may also limit the limit the risk for genetic predispositionsrisk for genetic predispositions such as such as heart disease, alcoholism, and certain heart disease, alcoholism, and certain cancers.cancers.

2.2. Environmental toxins such as UV Environmental toxins such as UV radiation and tobacco products can radiation and tobacco products can directly change our genesdirectly change our genes. Harmful . Harmful behaviors (such as smoking) and behaviors (such as smoking) and positive behaviors (such as using sun positive behaviors (such as using sun screen) increase or reduce the screen) increase or reduce the likelihood of genetic mutations from likelihood of genetic mutations from these toxins. The these toxins. The mutations may lead mutations may lead to cancers if protective genes are to cancers if protective genes are disrupteddisrupted..

Review Questions:Review Questions:1. Name two ways the symptoms of genetic 1. Name two ways the symptoms of genetic

disorders may be treated.disorders may be treated.Pain medication, physical therapy, dietPain medication, physical therapy, diet

2. What is gene therapy?2. What is gene therapy? use engineered cell invaders (such as a virus) in order to use engineered cell invaders (such as a virus) in order to actually replace the defective gene in target cells with a actually replace the defective gene in target cells with a functioning genefunctioning gene

3. Give an example of how diet can affect 3. Give an example of how diet can affect genes.genes.Can limit the risks of certain diseasesCan limit the risks of certain diseases

4. Identify two environmental toxins that may 4. Identify two environmental toxins that may affect genes.affect genes.UV radiation, tobacco smokeUV radiation, tobacco smoke