AP BIOLOGY Chapter 15 Chromosomal Basis of Inheritance

AP BIOLOGY Chapter 15 Chromosomal Basis of Inheritance Big Idea 3: Living systems store, retrieve, transmit and respond to information essential to life processes. http: //www. biochem. arizona. edu/classes/bioc 460/spring/rlm/genetics. jpeg

Essential knowledge 3. A. 3: The chromosomal basis of inheritance provides an understanding of the pattern of passage (transmission) of genes from parent to offspring. a. Rules of probability can be applied to analyze passage of single gene traits from parent to offspring. GENOTYPE TT = 25% Tt = 50 % tt = 25% PHENOTYPE 75% dominant trait 25% recessive trait Punnett by Riedell Aa. Bb. Cc. DD Probability of a. Bc. D ½ x ½ x 1 =1/8

Essential knowledge 3. A. 3. b. Segregation and independent assortment of chromosomes result in genetic variation. ~ The behavior of chromosomes during meiosis accounts for Mendel’s laws of segregation and independent assortment Evidence of student learning is a demonstrated understanding of each of the following: 1. Segregation and independent assortment can be applied to genes that are on different chromosomes. http: //bioap. wikispaces. com/file/view/crossing_over. gif/133299913/238 x 238/crossing_over. gif http: //bio 1151. nicerweb. com/Locked/media/ch 14/14_08 Independent. Assort. jpg

Essential knowledge 3. A. 3. b. Segregation and independent assortment of chromosomes result in genetic variation. Evidence of student learning is a demonstrated understanding of the following: 1. Segregation and independent assortment can be applied to genes that are on different chromosomes. http: //bio 1151. nicerweb. com/Locked/media/ch 14/14_08 Independent. Assort. jpg

Essential knowledge 3. A. 3. b. Segregation and independent assortment of chromosomes result in genetic variation. Evidence of student learning is a demonstrated understanding of each of the following: 2. Genes that are adjacent and close to each other on the same chromosome tend to move as a unit; the probability that genes will segregate as a unit is a function of the distance between them. The farther apart genes are on a chromosome the more likely they are to be separated during crossing over http: //anthro. palomar. edu/biobasis/images/linked_genes. gif http: //cnx. org/content/m 47304/latest/Figure_08_03_06. jpg

Many fruit fly genes were mapped initially using recombination frequencies T. H. Morgan did experiments with fruit flies to see how linkage affects the inheritance of two different characters ~ Linked genes that are close together on the same chromosome do not assort independently ~ Genes that assort independently are either: - on separate chromosomes OR - are far apart on the same chromosome Y II I X Short aristae 0 Long aristae (appendages on head) IV III Mutant phenotypes Black Cinnabar Vestigial Brown body eyes wings eyes 48. 5 57. 5 67. 0 Gray Normal Red body wings eyes Wild-type phenotypes 104. 5 Red eyes Copyright © 2002 Pearson Education, Inc. , publishing as Benjamin Cummings

Linkage Mapping: Using Recombination Data • Cross true breeding parents of different phenotypes • Cross heterozygous F 1 organisms with pure-breeding recessives (like a TEST CROSS) • Count recombinants (ones that look different from parental phenotype)

Essential knowledge 3. A. 3. b Evidence of student learning is a demonstrated understanding of each of the following: 3. The pattern of inheritance (monohybrid, dihybrid, sex-linked, and genes linked on the same homologous chromosome) can often be predicted from data that gives the parent genotype/ phenotype and/or the offspring phenotypes/genotypes. female flies with red eyes (wild type) male flies with white eyes The F 1 generation all had red eyes F 2 generation showed the 3: 1 red: white eye ratio, but only males had white eyes T. H. Morgan proposed that the white eye mutation was carried on X chromosome

Essential knowledge 3. A. 4: The inheritance patterns of many traits cannot be explained by simple Mendelian genetics. a. Many traits are the product of multiple genes and/or physiological processes. Evidence of student learning is a demonstrated understanding of the following: 1. Patterns of inheritance of many traits do not follow ratios predicted by Mendel’s Laws and can be identified by quantitative analysis, where observed phenotypic ratios statistically differ from the predicted ratios.

Different systems of sex determination are found in other organisms 22 + XX 22 + X 76 + ZW 76 + ZZ 16 16 (b) The X– 0 system (c) The Z–W system (Diploid) (Haploid) (d) The haplo-diploid system Temperature determination- some reptiles

Essential knowledge 3. A. 4: The inheritance patterns of many traits cannot be explained by simple Mendelian genetics. b. Some traits are determined by genes on sex chromosomes. To foster student understanding of this concept, instructors can choose an illustrative example such as: • Sex-linked genes reside on sex chromosomes (X in humans). • In mammals and flies, the Y chromosome is very small and carries few genes. • In mammals and flies, females are XX and males are XY; as such, X-linked recessive traits are always expressed in males.

Y chromosome-small & carries only a few genes http: //pageofmystery. com/ALPHAS/genetics/earhairbig. jpg Y linked traits show up ONLY in MALES EX: hairy pinna SRY gene Master control gene turns on other genes Creates a cascade of activation to make developing embryo into a MALE http: //www. nature. com/scitable/content/18935/pierce_4_10_large_2. jpg

X-Linked Genes Recessive genes carried on the X chromosome Red-green colorblindness Mutation in protein receptors in eye that distinguish colors Hemophilia Inability to make blood clotting factors Duchenne Muscular Dystrophy Change in muscle proteins; results early death http: //gizmodo. com/gadgets/peripherals/samsung-develops-lcd-for-colorblind-036306. php

X-linked traits show up more frequently in males The X chromosome in males. . . flies WITHOUT a copilot!

What’s the pattern: X-LINKED RECESSIVE traits ~ Show up more frequently in males because they have no back up X ~ Females need two recessive alleles to show the trait. ~ Females can be carriers for X linked traits ~ Male can never be carriers of X linked recessive traits AUTOSOMAL RECESSIVE traits ~ Both males and females can be carriers for autosomal recessive traits.

Essential knowledge 3. A. 4. The inheritance patterns of many traits cannot be explained by simple Mendelian genetics. • Some traits are sex limited • Expression depends on the sex of the individual Ex: milk production in female mammals pattern baldness in males. MALE PATTERN BALDNESS SEX LIMITED (SEX INFLUENCED) AUTOSOMALNOT ON A SEX CHROMOSOME BUT. . . SHOWS DIFFERENT PATTERN IN MALES & FEMALES BB or Bb = bald bb= not bald FEMALES BB = bald Bb or bb= not bald Almost like B is dominant in males and b is dominant in females

Essential knowledge 3. A. 3: The chromosomal basis of inheritance provides an understanding of the pattern of passage (transmission) of genes from parent to offspring. c. Certain human genetic disorders can be attributed to the inheritance of single gene traits or specific chromosomal changes, such as nondisjunction. To foster student understanding of this concept, instructors can choose an illustrative example such as: • Sickle cell anemia • Tay-Sachs disease • Huntington's disease • X-linked color blindness • Trisomy 21/Down syndrome • Klinefelter syndrome

AUTOSOMAL RECESSIVE Phenylketonuria-PKU Enzyme to break down phenylalanine is missing Build up in brain causes mental retardation Need diet low in proteins TAY SACHS Lysosomal storage disorder Fats aren’t broken down; build up in brain Cause blindness, retardation; early death More common in Jewish populations CYSTIC FIBROSIS Mutation in gene for Cl- ion transport Build up of mucous in body organs Digestive/respiratory problems More common in Caucasian populations http: //stores. pkuperspectives. com/catalog/PKU 2 web. jpg http: //tay-sachs-disease. wikispaces. com/file/view/bb_feb 2007_large. jpg/34183391/bb_feb 2007_large. jpg http: //www. medicalook. com/diseases_images/cystic_fibrosis. jpg

AUTOSOMAL DOMINANT (Homozygous Dominant = LETHAL) ACHONDROPLASIA “Dwarfism” Growth plates in long bones fuse too early HUNTINGTON’S Multiple CAG repeats result in neurological degeneration in middle age Hear song

AUTOSOMAL CODOMINANT SICKLE CELL ANEMIA Mutation in hemoglobin gene Causes red blood cells to change shape in low oxygen conditions More common in African Americans HETEROZYGOTE ADVANTAGE: 1 sickle cell allele/1 normal allele provides protection against MALARIA Watch a video about sickle cell and malaria

CLOSER LOOK AT RELATIONSHIP BETWEEN DOMINANCE AND PHENOTYPE REVEALS AN INTRIGUING FACT: DOMINANCE ? CODOMINANCE? INCOMPLETE DOMINANCE ? Depends on how you look at it!

Image from: http: //www. djsfoundation. org/images/Steeler%20 pics%20 Dylan. jpg TAY-SACHS DISEASE Human genetic disorder in which brain cells are unable to metabolize certain lipids because a crucial enzyme does not work properly. As these lipids build up in brain infant suffers seizures, blindness, loss of motor & mental function > > > leads to early death. At ORGANISMAL LEVEL acts as a recessive trait. Child with two copies of Tay-Sachs allele (tt-homozygous) has the disorder. Child with Tt or TT does not (COMPLETE DOMINANCE) At BIOCHEMICAL LEVEL- Tt individual has enzyme activity level in between the TT and tt person (INCOMPLETE DOMINANCE ? ) At the MOLECULAR LEVEL – Tt individual makes equal number of normal and dysfunctional enzyme molecules (CODOMINANT ? )

Alterations of Chromosome Structure A deletion occurs when a chromosome fragment lacking a centromere is lost during cell division. • This chromosome will be missing certain genes. • A duplication occurs when a fragment becomes attached as an extra segment to a sister chromatid. Images from: Biology; Campbell and Reese; Pearson Education, Inc. , publishing as Benjamin Cummings Slide from: Slide show by Dr. Chuck Downing

Alterations of Chromosome Structure Chromosomal translocations between nonhomologous chromosome are also associated with human disorders. Chromosomal translocations have been implicated in certain cancers, including chronic myelogenous leukemia (CML). CML occurs when a fragment of chromosome 22 switches places with a small fragment from the tip of chromosome 9. Normal chromosome 9 Reciprocal translocation Translocated chromosome 9 Philadelphia chromosome Normal chromosome 22 Translocated chromosome 22 http: //www. antigenics. com/diseases/images/philly_chrom. gif

Alterations of Chromosome Structure • An inversion occurs when a chromosomal fragment reattaches to the original chromosome but in the reverse orientation. See a Video • In translocation, a chromosomal fragment joins a nonhomologous chromosome. See a Video Slide from: Slide show by Dr. Chuck Downing Images from: Biology; Campbell and Reese; Pearson Education, Inc. , publishing as Benjamin Cummings

Duplications and translocations are typically harmful Cri du chat Is a disorder caused by a deletion in chromosome #5 • Mental retardation • Small head • Unusual facial features • “cat cry” http: //www. morfosa. org/medweb/patologi/bilder/cri-du-chat. gif

Enduring understanding 3. C: The processing of genetic information is imperfect and is a source of genetic variation. Essential knowledge 3. C. 1: Changes in genotype can result in changes in phenotype. c. Errors in mitosis or meiosis can result in changes in phenotype. Evidence of student learning is a demonstrated understanding of each of the following: 2. Changes in chromosome number often result in human disorders with developmental limitations, including Trisomy 21 (Down syndrome) and XO (Turner syndrome). [See also 3. A. 2, 3. A. 3] Normal Meiosis http: //web. udl. es/usuaris/e 4650869/docencia/gen_etica/meioferti 2. html Nondisjunction http: //www. tokyo-med. ac. jp/genet/anm/domov. gif

Nondisjunction – Failure of homologous chromosomes OR chromatids to separate at anaphase

Nondisjunction Results in ANEUPLOIDY = one or more chromosomes have extra or missing copies AFTER FERTILIZATION: Cell with only 1 copy of a chromosome instead of 2 = MONOSOMY Cell with 3 copies of a chromosome instead of 2 = TRISOMY

Down syndrome (Trisomy 21) http: //www. hadsa. org/ Most common chromosomal abnormality (1 in 800 births) Similar facial features Slanted eyes / Protruding tongue Mild to severe mental retardation 50% have heart defects that need surgery to repair Both older (35+ years) and younger (under 16 years) mothers are more at risk. http: //www. healthofchildren. com/images/gech_0001_0002_0_img 0096. jpg

Some individuals with Down syndrome have the normal number of chromosomes but have all or part of a third chromosome 21 attached to another chromosome by translocation. http: //content. answers. com/main/content/wp/en/thumb/f/f 5/180 px-Down_syndrome_translocation. png

Turner syndrome (X 0) http: //medgen. genetics. utah. edu/photographs/diseases/high/611. gif 1 in 5000 births Females have only one X chromosome Small size Broad chest Slightly decreased intelligence 35% have heart abnormalities Hearing loss common Reproductive organs don’t develop at puberty

http: //www. akdeniz. edu. tr/tip/histoloji/embrders_dosyalar/slide 0228_image 1186. jpg Klinefelter syndrome 1 in 2000 births live births Males have extra X chromosomes (Can be XXy, XXXy, or XXXXy) Taller than average Normal intelligence have male sex organs, but are sterile. may be feminine characteristics, Often not discovered until puberty when don’t mature like peers Presence of BARR BODIES

Image from Biology; Campbell and Reece; Pearson Prentice Hall publishing as Benjamin Cummings © 2006

Karyotype can show: • Sex of baby • Missing or extra chromosomes • Major deletions or translocations • Can’t see individual gene changes http: //content. answers. com/main/content/wp/en/thumb/f/f 3/220 px-Down_syndrome_translocation. png

Enduring understanding 3. C: The processing of genetic information is imperfect and is a source of genetic variation. Essential knowledge 3. C. 1: Changes in genotype can result in changes in phenotype. c. Errors in mitosis or meiosis can result in changes in phenotype. Evidence of student learning is a demonstrated understanding of each of the following: 1. Changes in chromosome number often result in new phenotypes, including sterility caused by triploidy and increased vigor of other polyploids. [See also 3. A. 2] Polyploidy -common among plants Ex: Strawberries = octaploid wheat = hexaploid Much less common in animals LETHAL in humans Polyploids are more nearly normal in phenotype than aneuploids. http: //tasty-dishes. com/data_images/encyclopedia/strawberry-03. jpg Copyright © 2002 Pearson Education, Inc. , publishing as Benjamin Cummings

POLYPLOIDY Organisms with more than two complete sets of chromosomes Can occur when a normal gamete fertilizes another gamete in which there has been nondisjunction of all its chromosomes. Results in triploid (3 n) zygote OR if 2 n zygote fails to divide after replicating its chromosomes Results in a tetraploid (4 n) embryo Copyright © 2002 Pearson Education, Inc. , publishing as Benjamin Cummings

If having extra chromosomes causes genetic problems, how come having two X chromosomes in females and one X in males is not a problem?

X-chromosome Inactivation In female cells ONE X chromosome is randomly switched off It condenses and forms a dense region in the nucleus called a BARR BODY http: //fig. cox. miami. edu/~cmallery/150/gene/barr. htm

CAT COLOR http: //www. eagle. ca/~roda/Rod. Mer. Arts/Swallow. Hill/Kiisu. html In cats the gene that controls color is carried on the X chromosome Tortoiseshell cats express different alleles in different cells FEMALE CATS: Female cat can have BOTH black and orange spots See a video http: //www. islandstrolling. com/mainland/peloponnes/photo/mystra_cat_white_orange_black. jpg

CAT COLOR http: //ascensionparish. net/forum/messages/14/2493. jpg MALE cats have only one X chromosome, so they can only have ONE COLOR of spots! THINK ABOUT IT? How many colors of spots could a male cat with Klinefelter syndrome have?

Images from: http: //www. fisterra. com/human/3 arte/pintura/temas/enanos. asp “La Monstrua Vestida” “La Monstrua Desnuda” Paintings in Prado Museum in Madrid by Juan Carrneño Miranda of a 5 year old girl named Eugenia Marinez Vallejo

PRADER-WILLI Syndrome Victor Age 1 Victor Age 2 Born floppy and pale At first refuse to nurse, but later eat until they become obese Tiny hands and feet Underdeveloped sex organs Mildly retarded Spectacular temper tantrums especially if refused food Exceptional proficiency with Jig-saw puzzles Missing piece of chromosome #15

ANGELMAN’S SYNDROME Taut, not floppy Thin Hyperactive Insomniac Small head Move jerkily like puppets Happy disposition Severely mentally retarded Rarer than Prader-Willi Missing SAME piece of Chromosome #15 Colin Farrell’s son has Angelman’s syndrome http: //www. usmagazine. com/colin_farrell_and_son

WHAT’S THE DIFFERENCE? • In Prader-Willi missing piece of #15 was from father • In Angelman’s, missing piece of #15 was from the mother How does a gene “remember” where it came from? GENOMIC IMPRINTING

EPIGENETICS “above genetics” Molecules sit on top of the genome Control which genes are ON or OFF http: //www. teachersdomain. org/assets/wgbh/biot 09_vid_epigenetics/biot 09_vid_epigenetics_l. jpg

GENOMIC IMPRINTING Involves the silencing of certain genes that are “stamped” with an imprint during gamete production so same allele (maternal or paternal) is expressed in all body cells • Involves methylation (-CH 3) (turns genes OFF) or demethylation (turns genes on) of cytosine nucleotides Several hundred mammalian genes, many critical for development, may be subject to imprinting. http: //www. scq. ubc. ca/wp-content/uploads/2006/08/methylation%5 B 1%5 D-GIF. gif

• In the new generation, both maternal and paternal imprints are apparently “erased” in gameteproducing cells. • Then, all chromosomes are reimprinted according to the sex of the individual in which they reside. • Imprinting is critical for normal development. Copyright © 2002 Pearson Education, Inc. , publishing as Benjamin Cummings

Addition or removal or “methyl tags” may be influenced by environment • Twins start with same methyl tags but become more different with age • Agouti rats – changing diet of pregnant mom can change expression of genes VIDEO http: //www. precisionnutrition. com/wordpress/wp-content/uploads/2009/12/Figure-3 -Agouti-mice. jpg

Addition or removal or “methyl tags” may be influenced by environment • • DIET STRESS EXERCISE CHEMICALS http: //www. naturepedic. com/blog/wp-content/uploads/2010/11/BPA_free_logo. jpg http: //www. knowabouthealth. com/wp-content/uploads/2010/06/mcdonalds_. jpg http: //emilyscarenhealth. wordpress. com/2011/10/04/attention-a-must-read-for-smokers/

GENOMIC IMPRINTING • Tags Maternal/Paternal chromosomes • Differentiation of cell types (blood, skin, etc) • Embryonic development • Changes in puberty, pregnancy, aging • X chromosome inactivation (Barr bodies) • differences can lead to diseases (cancer) and genetic disorders http: //www. molekularbiologie. abi. med. uni-muenchen. de/ueber_uns/schotta/index. html

LINKS TO CANCER BRCA = tumor suppressor gene If it’s turned OFF cancer cells are NOT repaired and can grow into a tumor http: //www. landesbioscience. com/journals/epigenetics/

Fragile X syndrome, which leads to various degrees of mental retardation, also appears to be subject to genomic imprinting. • This disorder is named for an abnormal X chromosome in which the tip hangs on by a thin thread of DNA. Image from: http: //www. lakeforest. edu/images/user. Images/eukaryon/Page_6605/Fig-1. jpg • This disorder affects one in every 1, 500 males and one in every 2, 500 females. • Inheritance of fragile X is complex, but the syndrome is more common when the abnormal chromosome is inherited from the mother. • This is consistent with the higher frequency in males. • Imprinting by the mother somehow causes it. Slide Copyright © 2002 Pearson Education, Inc. , publishing as Benjamin Cummings

SO WHAT? • It’s not just a MOM thing • Epigenetic therapy in future ? ? • How does what you do affect your kids’ and grandkids’ epigenome? We are just beginning to understand. . . http: //www. naturepedic. com/blog/wp-content/uploads/2010/11/BPA_free_logo. jpg http: //www. knowabouthealth. com/wp-content/uploads/2010/06/mcdonalds_. jpg http: //emilyscarenhealth. wordpress. com/2011/10/04/attention-a-must-read-for-smokers/

c. Some traits result from nonnuclear inheritance. Evidence of student learning is a demonstrated understanding of each of the following: 1. Chloroplasts and mitochondria are randomly assorted to gametes and daughter cells; thus, traits determined by chloroplast and mitochondrial DNA do not follow simple Mendelian rules. 2. In animals, mitochondrial DNA is transmitted by the egg and not by sperm; as such, mitochondrial-determined traits are maternally inherited. http: //faculty. clintoncc. suny. edu/faculty/michael. gregory/files/Bio%20100%20 Lectures/meiosis/img 025. gif

EXTRANUCLEAR GENES The inheritance of traits controlled by genes present in the chloroplasts or mitochondria Depends solely on the maternal parent because the zygote’s cytoplasm comes from the egg EX: Variegated leaves result from mutations in pigment genes located in plastids inherited from mother Image from Biology; Campbell and Reece; Pearson Prentice Hall publishing as Benjamin Cummings © 2005

EXTRANUCLEAR GENES Some diseases affecting the muscular and nervous systems are caused by defects in mitochondrial genes that prevent cells from making enough ATP http: //www. ncl. ac. uk/nnp/research/mrg/advice/inheritance. htm

MITOCHONDRIAL DISEASES are RARE Accumulation of mitochondrial mutations may play role in aging process, diabetes, heart disease, Alzheimer’s • EX: mitochondrial myopathy • weakness, • intolerance of exercise • muscle deterioration http: //employees. csbsju. edu/hjakubowski/classes/ch 331/oxphos/mitochondria. gif

Essential knowledge 3. A. 3: d. Many ethical, social and medical issues surround human genetic disorders. To foster student understanding of this concept, instructors can choose an illustrative example such as: • Reproduction issues • Civic issues such as ownership of genetic information, privacy, historical contexts, etc. http: //media 2. abc 2 news. com//photo/2012/11/22/DNA_Supreme_ourt_109850000_20121122000601_320_240. JPG http: //www. genewatch. org/uploads/865 d 357353 e 86 dfc 74 ba 59 e 18 bffed 98/Gen. Testing. gif http: //www. rainydaybooks. com/files/rainyday/files/Rebecca. Skloot. jpg