Beyond Mendel… Mutations, Gene Linkage, Gene-Mapping, Sex Linkage, Polygenic Traits, Non-disjunction, disorders, Prenatal Diagnosis, Pedigree Analysis

Back to “Beyond Mendel” Mutations Definition Mutations in Genes Point Mutations Frame-shift Mutations Mutations in Chromosomes Deletion Duplication Inversion Translocation Back to “Beyond Mendel”

Mutations Definition: A change in the genetic material (DNA or RNA) of a cell Somatic: If it occurs in body cells, it can’t be passed on to next generation Germ-line: If it occurs in gametes, it can be passed on to next generation Back to Mutations

Mutations in Genes Point Mutation: Affects one nucleotide (One nucleotide is replaced by another) - three types of point mutations let’s look at one example… Missense mutations: Code for a different A.A. (ex. sickle-cell anemia) Nonsense mutations: Code for a stop codon Silent mutations: Codes for same amino acid

Mutations in Genes Frameshift Mutation: An insertion or deletion that shifts the reading frame Example of Insertion: TA Example of Deletion: CGCATGGAATACC TEF THE H FAT ATC CAT ATA TET ATE THE HER RAT AT Back to Mutations T

Deletion: A segment of the chromosome is removed (not just one nuclotide) A B C D E F G H A B C E F G H 2. Duplication: A segment of the chromosome is repeated A B C D E F G H A B C B C D E F G H 3. Inversion: A segment within a chromosome is reversed 4. Translocation: A segment from one chromosome moves to another, non-homologous one A B C D E F G H A D C B E F G H Back to Mutations Examples: Deletion: Duchenne Muscular Dystrophy (on X chromosome) Duplication: Huntington’s Disease (Chromosome 4) Inversion & Translocation: Phenotypically normal, but increased risk of having gametes with abnormal numbers of chromosomes A B C D E F G H M N O C D E F G H M N O P Q R A B P Q R

Linked Genes In flies, grey bodies (G) and normal-wing size (W) are dominant to black bodies (g) and small wing size (w). In this cross will the F1 grey flies always have normal wings and will black flies always have small wings?

Actual Results WHY? 8.5% 8.5% 41.5% 41.5% 41.5% 41.5% No! However, most of the F1 flies will have either a grey body and normal wings OR a black body with small wings, like their parents Will the F1 grey flies always have normal wings and will black flies always have small wing sizes?

Back to “Beyond Mendel” Linked Genes The genes for body color and wing size are “linked”,meaning they are found on the same chromosome. They will most likely be inherited together and will not undergo Mendel’s Law of . cross over segregates the linked genes g g G G Independent Assortment W w W w unless Back to “Beyond Mendel”

Back to “Beyond Mendel” Gene Mapping Genes that are closer together on the same chromosome are less likely to cross over, therefore segregate. Genes that are farther apart on the same chromosome are more likely to cross over and segregate Genes that are on different chromosomes will always segregate independently Grey Body Black Body Normal wings Small wings Back to “Beyond Mendel”

Sex-Linkage or (X-linked) In fruit flies, (R) is the dominant gene for red eyes, and (r) is the recessive gene for white eyes. The gene is found on the “X” chromosome. This is considered X-linked. Does the gene for eye color exist on the “Y” chromosome? Why or why not? These are the X and Y chromosomes of a male fly. How is the Y chromosome different from the X? R r r XX XY What would be the phenotype of this female fly? What would be the phenotype of this male fly?

Sex-Linkage or (X-linked) Watch this video to clarify your knowledge of sex-linked traits When genes are sex-linked, we include the X and Y as part of their genotype. For example, the allele for red eye is not “R” but is written as XR. How would you write the allele for white eye? Xr

White board practice What is the possible genotype(s) for this red-eye fly if it is a female? What is the possible genotype for this red-eye fly if it is male? Answer the above questions again for this fly.

White board practice You work in a fruit fly lab and you cross a heterozygote red-eye female with a red-eye male. Predict the F1 offspring using a punnett square. What is the phenotypic ratio?

White board practice Balding is a trait that can occur in females although it is rare. What genotype must a female be in order to be bald? Why, then, is balding a trait more common in men then women? Adult on-set male-pattern baldness is thought to be a sex-linked recessive trait. Your dad is going bald and your mother complains that if you or your go bald the gene for baldness is your dad’s fault. Use a Punnett square to prove to your mother that the gene would actually come from her side.

Sex-linked or X-linked Time to reinforce your knowledge with a lab! Back to “Beyond Mendel”

Polygenic Traits Definition: Traits controlled by two or more genes Examples: Skin color, height

Back to “Beyond Mendel” Polygenic Traits Skin Color Height What about our height? Does it form the same pattern? Activity: Let’s create a histograph of the height of all students in class! Back to “Beyond Mendel”

Non-disjunction Disorders Definition: When members of homologous chromosomes fail to separate during Meiosis I – or – when sister chromatids fail to separate during Meiosis II. Examples: Down Syndrome, Turner’s syndrome, Klinefelter’s syndrome Meiosis I Meiosis II Abnormal Gametes Back to “Beyond Mendel” Normal Gametes

Prenatal Diagnosis: Amniocentesis 1. Amniotic fluid withdrawn Fetus (14 – 16 weeks) 2. Centrifuge Fluid Several weeks later Fetal Cells Placenta 3. Karyotype Uterus Cervix Cell culture

Prenatal Diagnosis: Chorionic villus sampling (CVS) 1. Suction tube inserted through cervix Fetus (8 – 10 weeks) Fetal cells Placenta Chorionic villi 2. Karyotype Several hours

Interpret these karyotypes Sex: Male

Interpret these karyotypes Klinefelter’s syndrome

Interpret these karyotypes Down Syndrome

Genetic Disorder Brochure Assignment You will be assigned one of the following genetic disorders: 1) Color Blindness 2) Klinefelter’s syndrome 3) Cystic Fibrosis 4) Marfan’s Syndrome 5) Down’s Syndrome 6) Patou’s Syndrome 7) Duchenne Muscular Dystrophy 8) Phenylketonuria 9) Edward’s Syndrome 10) Sickle Cell Anemia 11)Fragile X Syndrome 12) Tay-Sachs Disease 13)Hemophilia 14) Turner’s Syndrome 15)Huntington’s Disease 16) Werner’s Syndrome You will work alone on this project. If you have a disease that a classmate has, you may collaborate during research, but you must each create your own brochure and present it in a different way. Be careful of plagiarism! Plagiarised projects will automatically a zero, possibly even a double zero score!

Generally: A genetic family tree A Pedigree is… Generally: A genetic family tree Specifically: It is a chart of the genetic history of family over several generations.

Pedigree A = tongue roller a = can not roll tongue Aa ? aa ? ? ? ? aa Can you figure out the rest of the genotypes on your own? male Mating couple female Shaded = trait being followed Children/Siblings

Other Pedigree Symbols Examples of connected symbols: Fraternal twins Identical twins

Other Pedigree Symbols Affected X-linked Autosomal carrier Deceased Back to Overview

Interpreting a Pedigree Chart Determine if the pedigree chart shows an autosomal or X-linked disease. If most of the males in the pedigree are affected the disorder is . If it is a 50/50 ratio between men and women the disorder is . X-linked autosomal

Example of Pedigree Charts Is it Autosomal or X-linked?

Answer Autosomal

Interpreting a Pedigree Chart Determine whether the disorder is dominant or recessive. If the disorder is dominant, one of the parents must have the disorder. If the disorder is recessive, neither parent has to have the disorder because they can be heterozygous.

Example of Pedigree Charts Dominant or Recessive?

Answer Dominant

Example of Pedigree Charts Dominant or Recessive?

Answer Recessive

Summary Pedigrees are family trees that explain your genetic history. Pedigrees are used to find out the probability of a child having a disorder in a particular family. To begin to interpret a pedigree, determine if the disease or condition is autosomal or X-linked and dominant or recessive.