* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Ch 14- Human Heredity
Molecular cloning wikipedia , lookup
Quantitative trait locus wikipedia , lookup
Cancer epigenetics wikipedia , lookup
Minimal genome wikipedia , lookup
DNA vaccination wikipedia , lookup
Epigenetics of neurodegenerative diseases wikipedia , lookup
Biology and consumer behaviour wikipedia , lookup
Cre-Lox recombination wikipedia , lookup
DNA supercoil wikipedia , lookup
Genealogical DNA test wikipedia , lookup
Gene therapy wikipedia , lookup
Skewed X-inactivation wikipedia , lookup
Genomic library wikipedia , lookup
Human genome wikipedia , lookup
Genetic engineering wikipedia , lookup
Gene expression profiling wikipedia , lookup
Non-coding DNA wikipedia , lookup
Polycomb Group Proteins and Cancer wikipedia , lookup
Gene expression programming wikipedia , lookup
Genome evolution wikipedia , lookup
Nutriepigenomics wikipedia , lookup
Dominance (genetics) wikipedia , lookup
Extrachromosomal DNA wikipedia , lookup
Site-specific recombinase technology wikipedia , lookup
Genomic imprinting wikipedia , lookup
Vectors in gene therapy wikipedia , lookup
Helitron (biology) wikipedia , lookup
Therapeutic gene modulation wikipedia , lookup
Point mutation wikipedia , lookup
Cell-free fetal DNA wikipedia , lookup
Epigenetics of human development wikipedia , lookup
Y chromosome wikipedia , lookup
History of genetic engineering wikipedia , lookup
Neocentromere wikipedia , lookup
Genome (book) wikipedia , lookup
X-inactivation wikipedia , lookup
Artificial gene synthesis wikipedia , lookup
Designer baby wikipedia , lookup
14-1 Human Heredity Vocabulary: •Karyotype •Sex chromosome •Autosome •Pedigree •Polygenic •Carrier Key Concept: How is sex determined? How do small changes in DNA cause genetic disorders? Human Chromosomes • To examine human chromosomes, biologist photograph cells in mitosis when the chromosomes are fully condensed • Cut out the chromosomes from the picture and group them together in pairs • This type of picture is called a KARYOTYPE Karyotypes • • A karyotype can tell you THREE things: 1. Sex (male or female) 2. Irregular numbers of chromosomes 3. Any mutations in the chromosomes Basically: all the chromosomes in a cell are displayed and can be examined for any abnormalities Remember… • Humans have 46 chromosomes (23 pair) • 2 of them are sex chromosomes they determine what sex you are – XX = female – XY = male • 44 of them are autosomes they do not determine what sex you are Who determines the sex of a child? The mother or the father? THE FATHER!!!! Why does the father determine the sex of the offspring??? • Mom is XX, she can donate either one X chromosome or the other X chromosome • Dad is XY, he can donate either an X chromosome or a Y chromosomes. • If the offspring receives the father’s X, it is female • If the offspring receives the father’s Y, it is male The Y chromosome • If a Y chromosome is present, the person is male • X chromosomes contain genes necessary for growth/development • No cases of a person born with being 45,0Y – Probably spontaneously aborted (miscarriage) Human Genes • The human genome is the complete set of genetic information – Determines characteristics such as eye color and how proteins function within cells Recessive and Dominant Alleles • Some common genetic disorders are autosomal recessive – This means that you need two recessive alleles (on any of the 44 chromosomes—NOT the sex chromosomes) to express the disease • EX: Cystic Fibrosis • Other genetic disorders are autosomal dominant – Only one allele is needed for the trait to be expressed • EX: Huntington’s Disease From Gene to molecule • In both cystic fibrosis and sickle cell anemia, a small change in the DNA of a single gene affects the structure of a protein, causing a serious genetic disorder Cystic Fibrosis • Caused by a recessive allele on chromosome #7 – It is an autosomal genetic disorder • Causes digestive and respiratory problems • Death around 20-30 years of age • How does it happen? – Three bases are deleted from the protein, which removes one amino acid – The protein cannot fold properly anymore, and is destroyed – Result: airway is clogged with mucus Sickle Cell Anemia • One DNA base has been changed • Amino acid is valine, instead of glutamic acid • Result=Abnormal hemoglobin Pedigree Chart • Shows how a trait is transmitted from generation to generation • Each row is a generation • Circles represent females • Squares represent males – Shaded in: person expresses that trait – Half shaded in: person is only a carrier – Clear: person does not carry or express that trait Definitions • Carrier= a person who carries the allele for the trait but does not express it • EX: Cystic Fibrosis is an autosomal recessive disorder – Carrier’s genotype= Ff – For a person to have Cystic Fibrosis (genotype=ff), he or she must have inherited an “f” from both parents – Therefore, BOTH parents must be carriers (both Ff) • Can’t trace every human trait through a pedigree because some genes are polygenic – – – – Shape of your eyes Shape of your ears Height Eye color • Also, phenotype is influenced by your environment (ex: nutrition & exercise) – Average height is 10cm more than it was in the 1800’s in the US & Europe due to nutritional improvements – Genes that are denied a proper environment in which to reach full expression in 1 generation, can achieve full potential in a later generation (genes are inherited, the environment is not) What makes an allele dominant or recessive? • Gene=sequence of DNA that codes for a protein • Usually: – Dominant alleles code for the correct production of that protein – Recessive alleles code for no/wrong protein production – Heterozygous condition—the normal (dominant) allele will still cause correct protein production Example • Cystic fibrosis heterozygotes (Ff) – just one copy of the normal (dominant) allele is enough to supply the cell with the proper proteins to function. – Because of this, the normal allele is considered dominant over the recessive allele • Therefore, a person who is heterozygous does not suffer from Cystic Fibrosis Review… If a person is a carrier for a trait, what does that mean? What is the difference between an autosome and a sex chromosome? • They have the allele for the trait but do NOT express it • Sex chromosome determines the individual’s sex (2), while autosomes are the rest of the chromosomes (44) Human Blood Groups Blood Groups • Human blood comes in a variety of genetically determined blood groups • Using the wrong blood during a blood transfusion can be fatal • A number of genes help determine blood type but we will focus on two: – ABO blood groups – Rh blood groups Blood Groups—the easy one first • The Rh blood group is determined by a single gene with 2 alleles—positive and negative • The positive allele is dominant • You need two Rh- alleles (Rh-/Rh-) to be Rh negative ABO Blood Groups • This is a case of multiple alleles • There are 3 alleles for this gene—A, B, and O. • AND…A and B are codominant! • O is recessive to A and B • Alleles A and B produce antigens (which are carbohydrates) on the surface of red blood cells • O produces NO antigens ABO Blood Groups—the wrong blood can be FATAL • Antigens are recognized by the immune system and induce an immune response • If the wrong blood is transfused, the body will respond to these antigens by producing antibodies – Antibodies are named for what they attack • Antibodies bind to the foreign molecule (the antigen) and blood clumping will occur, which leads to blood clotting, which leads to death ABO Blood Groups • If you have blood type A, then you have: – The “A” antigen on the surface or your RBCs – You have anti-B antibodies – You can receive type A blood and type O blood • Remember: Your antibodies are named for what they attack—so if you received type AB or type B blood then clumping would occur. ABO Blood Groups • Try this cross • Cross a person who’s genotype is AA with a person who is AB. • Give the possible genotypes and phenotypes • Cross a person who’s genotype is AA with a person who is AB. • Gametes= A, A and A, B • Cross: A A A B AA AB AA AB • Genotypes= ½ AA, ½ AB • Phenotypes = ½ A, ½ AB 14-2 Human Chromosomes (and 12-4) Vocabulary: • Sex-linked gene • Sex-influenced gene • Sex-limited gene • Nondisjunction Key Concepts: • Why are sex-linked disorders more common in males than in females? • What is nondisjunction, and what problems does it cause? Lou Gehrig: died at 37 of ALS Human Chromosomes • Your chromosomes contain about 30,000 genes and 46 chromosomes – Once thought to be over 100,000 genes • That’s about 3 billion base pairs • Remember: genes on the same chromosome are linked together – They tend to be inherited together Human Genes & Chromosomes • Chromosomes 21 & 22 are the smallest human autosomes – Chromosome 22 contains approximately 43 million DNA bases (approx. 545 genes) – Chromosome 21 contains approximately 32 million DNA bases (approx.225 genes) • 1 of these genes is associated with ALS (Amyotrophic Lateral Sclerosis) • Causes a progressive loss of muscle control due to the destruction of nerves in the brain and spinal chord Sex Linked Genes • What are linked genes? • They can be separated during meiosis through CROSSING OVER • Genes carried on the X or Y chromosome are sex linked because they are on the sex chromosomes • Many sex-linked genes are found on the X-chromosome Sex Linked Genes • The X chromosome has many genes that are important for growth and development • The Y-chromosome only contains a few genes • All X-linked traits are expressed in males • WHY??????? • Males only have 1 copy of the X chromosome, while females need 2 copies of the defective gene Sex-Linked Gene Disorders Colorblindness • 3 human genes associated with color vision are located on the X-chromosome • In males, a defective version of any one of these produces colorblindness • Females must receive 2 copies of the allele to be colorblind CXc X CY XCXC X XcY The Test http://www.toledo-bend.com/colorblind/Ishihara.html Sex-Linked Gene Disorders cont. 2. Hemophilia • 2 important genes on the X-chromosome that code for proteins control blood clotting • A recessive allele in either of these 2 genes may lead to hemophilia – – “bleeders disease” Injections of normal clotting proteins prevent death Sex-Influenced Genes • A person’s phenotype is affected by their sex • Ex: Pattern Baldness WOMEN: BB: not bald MEN: BB: not bald Bb: not bald Bb: bald bb: bald bb: bald X-Chromosome Inactivation • Females have 2 X-chromosomes… if 1 is enough for males, how does the cell “adjust” to the extra x-chromosome in females? • One X-chromosome is randomly switched off – Condenses and is called a Barr body Chromosomal Disorders • Most of the time, the mechanisms that separate human chromosomes in meiosis work very well, but things can go wrong • The most common error: NONDISJUNCTION – The chromosomes fail to separate – The result? Abnormal numbers of chromosomes Nondisjunction Prefixes: dis = absence of / opposite of non = not Root Word: Junction = joining together • disjunction = the act of separating • nondisjunction = the act of not separating Examples of Chromosomal Disorders • • • • Down Syndrome Klinefelter’s Syndrome Turner’s Syndrome Triple X Syndrome Examples of Nondisjunction resulting in Chromosomal Disorders • Down's Syndrome: 47 chromosomes with 3 #21 chromosomes. • Triple-X Syndrome: 47 chromosomes caused by 3 X chromosomes. • Klinefelter's Syndrome: 47 chromosomes caused by 2 X chromosomes and 1 Y chromosomes. • Turner's Syndrome: 45 chromosomes with 1 X chromosome (caused by the absence of one of the X chromosomes or a Y chromosome). Chromosomal Mutations (from 12-4) • Chromosomal Mutation – – – – Deletion Duplication Inversion Translocation Chromosomal Mutation (structural change) • Deletion: lose all or part of a chromosome ABC-DEF AC-DEF • Duplication: segment of a chromosome is repeated ABC-DEF ABBC-DEF Chromosomal Mutation (structural change) • Inversion: chromosome segment becomes oriented in reverse direction ABC-DEF ABE-DCF Chromosomal Mutation (structural change) • Translocation: part of 1 chromosome breaks off & attaches to another nonhomologous chromosome (segment is usually exchanged) ABC-DEF ABC-JKL GH-IJKL GH-IDEF Chromosomal Mutation (change in number) • If an organism is born with the incorrect number of chromosomes – Ex: 47 human chromosomes instead of 46 • Result of nondisjunction Down Syndrome • 3 copies of chromosome #21 • 1 in 800 babies in the US is born with this disease • produces mild to severe mental retardation • why should an extra copy of one chromosome cause so much trouble? Klinefelter’s Syndrome • This is a sex chromosomal disorder associated with males. • Nondisjunction causes an extra X chromosome to be passed along during meiosis (XXY). • Resulting male cannot reproduce • Cases have been found in which individuals were (XXXY) or (XXXXY) Turner’s Syndrome • This is a sex chromosomal disorder associated with females. • Nondisjunction causes offspring to inherit only one X chromosome (genotype = XO). • Resulting female is sterile due to underdeveloped sex organs. 14-3 Human Molecular Genetics DNA FINGERPRINTING • DNA fingerprinting is a technique developed to analyze sections of DNA that have little or no known function. – these areas vary widely from one individual to another. • This technique can be used to identify individuals based on banding patterns in the resulting DNA fragments • uses restriction enzymes – proteins that cuts DNA at specific sites along the nucleotide chain (cuts at specific base pairs). • Is used to determine paternity or match a suspect to a crime scene (like on CSI!) THE PROCESS 1. human DNA is cut with restriction enzymes; this produces DNA fragments of different lengths 2. mix the DNA fragments with a probe that glows in UV light (the probe will stick to certain segments of DNA) 3. run the DNA fragments through a clear gel DNA goes in wells at the top negative end •DNA has a "-" charge DNA will move to the "+" end of the gel positive end **smaller fragments will travel through the gel faster 4. Smaller fragments of DNA will travel through the gel faster (remember the gel is porous). Large DNA fragment Small DNA fragment negative end positive end 5. In order to see these fragments, the gel is viewed under UV light. The result: The DNA fragments with the probe attached will glow & you will see a banding pattern **Because each person's DNA is different, the restriction enzyme will cut the DNA in different places for different people and every person will have a different band pattern. DNA_DetectivePC.exe Gene Therapy • Gene therapy is the process of changing the gene that causes a genetic disorder. This way, the body can make the correct protein or enzyme it needs which eliminates the cause of the disorder. • 1st attempt to cure a genetic disorder by gene transfer: 1990 – Then, 1999: French girl apparently cured of an inherited immune disorder after cells from her bone marrow were removed, modified in the laboratory, and then placed back in her body • Uses a vector to get the “new” DNA inside your cell viruses are often used cause they infect cells easily. How does it work?…. 1. The virus DNA is modified so it doesn’t cause disease 2. DNA containing “good” gene is spliced to viral DNA 3. The patient is then infected with this newly modified virus particles which should carry the “good” gene into the cells and correct the disorder. Gene therapy today remains a high risk,experimental procedure. Ethical Questions raised as we learn more about the human genome and gene therapy: 1. If we can manipulate genes to cure disease, does this also give us the right to engineer our bodies? (determine eye color, whether you are tall/short, hair color, sex, blood type...) 2. What will be the consequences if biologists successfully clone human beings? Science meets Hollywood: Issues like these were the basis of the movie, GATTACA Review… What is the purpose of gene therapy? What is a restriction enzyme? Gene therapy is a process designed to change (replace) the damaged or defective gene with a normal, functional A restriction enzyme is a protein that cuts DNA at specific sites along the nucleotide chain (cuts at specific base pairs). gene.