INSTRUCTIONAL TEAM: Bernadette Manzo & Jill Barnholtz-Sloan, PhD

Cleveland, Ohio

Title: Using pedigrees to determine patterns of inheritance of common traits. Targeted state standard: Explain the genetic mechanisms and the molecular basis of inheritance Performance indicators:

(1) Unit of hereditary information is called a gene, occurs in different forms called alleles (2) Mendelian and non-Mendelian genetic concepts to explain inheritance

Student misconceptions / holes in their knowledge: Truly no understanding of inheritance Do not know how to read a pedigree and interpret the information Do not grasp dominant versus recessive Major scientific concepts to be presented in flow order: (EXPLAIN) Prerequisite knowledge: meiosis/mitosis; DNA structure - Gene – unit of hereditary information - Allele - Mendelian genetics - Inheritance patterns (dominant, recessive – trait and disease examples; hitchhikers thumb,

widow’s peak, attached earlobe, face freckles, CF, Huntingtons disease, blood type) - Dominance - Polygeneic traits (trait and disease examples; hair color, height, wearing glasses, eye color,

skin color, cancer, diabetes; gene-gene and gene-environment (?)) - Pedigrees (how to draw one and how to read/interpret; first degree versus second degree

relatives) Learning outcomes / objectives:

(1) Understand what a gene is and where you get your genes from. (2) Interpret information on a given pedigree. (3) Construct a pedigree based on family information related to a particular trait and interpret

inheritance pattern. Skills used by students:

(1) Data collection (2) Pedigree construction (3) Pedigree interpretation/analysis

Basic structure: ENGAGE: Show picture of celebrity with one of the traits of interest Week 1: Pre-assessment and communication about results. Lecture/Lesson (making up own

curriculum materials); Pedigree demonstration; Homework assignment given (EXPLAIN) Week 2: Hands-on activity (described in detail below) in class based on homework assignment

(height, hitchhikers thumb, widow’s peak, attached earlobe) – Construct a pedigree using materials given to them (EXPLORE and EXPLAIN); In small groups each student will choose one trait and explain their pedigree and the traits inheritance pattern to the other students in the group (EVALUATE); Post-assessment (EVALUATE)

- if adopted or without biological family, do best friend’s family or a fictional family Week 3: Further communication and final write-up Extensions / follow-up: Based on pedigree activity construct a Punnet square and see if observed

probability matched up to expected probability, i.e. chi-square; genetic counseling; genetic testing; Wisconsin fast plants (EXTEND)

Curriculum materials to be used:

(1) Lesson/lecture designed by instructional team (2) Materials for hands-on activity designed by instructional team

ASSESSMENT STRATEGY Pre-assessment: (EVALUATE) Quiz consisting of 5 questions:

(1) What is a gene? (2) Where do you get your genes from? (3) Is every disease caused by your genes? (4) What is a pedigree? (5) Why is a pedigree useful?

Lesson/lecture will be modified accordingly based on the results.

Post-assessment: (EVALUATE) Quiz consisting of 5 questions:

(1) What is a gene? (2) Where do you get your genes from? (3) Is every disease caused by your genes? (4) What is a pedigree? (5) Why is a pedigree useful?

Formative assessment: Observing and guiding during hands-on activity (EXPLAIN) Summative assessment: Having student explain a trait within their pedigree including inheritance pattern (EVALUATE)

PARTNERSHIP STRATEGY In Classroom time and implementation of teaching plan will occur in the month of February 2009 (weeks 1-4 as outlined above) August 2008 – December 2008

- email communication once a week - in person meeting once a month - development and finalization of lesson/lecture and plan for hand-on activity through

email and discussion as needed - JBS student will assist in development of hands-on activity materials and homework

worksheet No current plans for writing a scientific paper or grant; may change in the future

The Human Genome

and Heredity

Jill Barnholtz-Sloan, Ph.D.

Assistant Professor

Case Western Reserve University School of Medicine

Introduction

�What is the Human Genome Project?�What is a genome?

�What is a chromosome?

�What is DNA?

�What are genes and proteins?

�What is mitosis and meiosis?

�What is Heredity?�Dominant, recessive, X-linked, sporadic

�How do I draw a pedigree?

The Human Genome Project� Begun formally in 1990, the project originally was planned to last 15 years, but because of rapid technological advances the expected completion date is sometime in 2003.

� GOALS:

� identify all the approximate 30,000 genes in human DNA,

� determine the sequences of the 3 billion chemical base pairs that � determine the sequences of the 3 billion chemical base pairs that make up human DNA,

� store this information in databases,

� Improve tools for data analysis,

� transfer related technologies to the private sector, and

� address the ethical, legal, and social issues (ELSI) that may arise from the project.

� To help achieve these goals, researchers also are studying the genetic makeup of several nonhuman organisms.

What is a Genome?�A genomegenome is all the DNA in an organism,

including its genes.

�Genes carry information for making all the

proteins required by all organisms.

�Genes make up approximately 2% of the �Genes make up approximately 2% of the

entire genome (~30,000 genes total).

�The rest of the genome is made up of noncoding

regions.

�Made up of 3 billion pairs of DNA subunits or

bases: A, C, T and G.

Comparing Genome and

Chromosome SizesGenome or ChromosomeGenome or Chromosome Number of bases (A,C,T,G)Number of bases (A,C,T,G)

Escherichia coli (bacterium) genome 4.6 million

Yeast chromosome 3 350,000

Largest yeast chromosome 5.8 million

Entire yeast genome 5.8 million

Smallest human chromosome (Y) 50 million

Largest human chromosome (1) 250 million

Entire human genome 3 billion

What is a chromosome?�Long thread-like structure that is composed of DNA.�Found in the nucleus of every cell.

�Trillions of cells in the human body.

�Carries part or all of the genetic information of an organism.organism.

�Humans have 23 pairs of chromosomes23 pairs of chromosomes(i.e. 46 chromosomes).

�22 autosomal (non-sex) pairs and 1 sex pair.

�XX-Female; XY-Male

�X always inherited from mother; either X or Y from father

Chromosome

Centromere

Chromosome

Telomere

What is a chromosome? (cont.)

�They are numbered 1-22 in order of size and then the two sex chromosomes.

�Each chromosome has specific pattern of “bands” which can be stained and studied.� Karyotype analysis

Source: Wisconsin State Laboratory of Hygiene

Down’s Syndrome

�Three copies

of

chromosome

21.

Source: Wisconsin State Laboratory of Hygiene

What is DNA?

��DNADNA is the molecule of life.

�DNA is a double-helix structure.

�DNA is made up of four similar chemicals (called bases and abbreviated A, T, C, and A, T, C, and GG) that are repeated millions or billions of GG) that are repeated millions or billions of times throughout a genome.

�As and Ts pair together and Cs and Gs pair together.

�Discovered in 1953 by James Watson and James Watson and Francis CrickFrancis Crick; Nobel Prize winners in 1962

Watson and Crick, 1953

What is DNA? (cont.)

�The particular order of As, Ts, Cs, and Gs is

extremely important.

�DNA becomes altered because of �DNA becomes altered because of

(1) mutationsmutations in base pairs and combinations of

base pairs and

(2) recombinationrecombination events that occur during meiosis.

Marker 1 has alleles

a and b

Marker 2 has alleles

c and d

Marker 3 has alleles

e and f

After the DNA

replicates, markers 2 replicates, markers 2

and 3 exchange

information,

Or recombination has

occurred between

markers 2 and 3.

What are Genes and Proteins?

��GenesGenes encode proteinsproteins....proteins then perform

life functions.

�Determines how the organism looks, how well its body

metabolizes food or fights infection, and sometimes even

how it behaves, etc..how it behaves, etc..

�Proteins are large, complex molecules.

�They are made up of series of codonscodons (sets of

three base pairs) that then specify which amino amino

acidacid is required to make that protein.

�Protein coded by the average gene is 3000 base pairs,

which means it is made up of 1000 amino acids.

What is Mitosis and Meiosis?�Mitosis and Meiosis are types of cell cell

divisiondivision.

�This is how we end up having 3 trillion cells

when we started from one cell!

�A “mother” cell divides to make TWO

“daughter” cells just like itself and then those

two cells divide to make FOUR cells and so

on.

What is Mitosis and Meiosis?

��MitosisMitosis: 2 cells created; each cell has TWO complete sets of chromosomes (DiploidDiploid)-ONLY 1 cell division.�Used to create all cells in body except reproductive cells.

��MeiosisMeiosis: 4 cells created; each cell has ONE complete set of chromosomes (HaploidHaploid)-TWO cell divisions.�Used only to create the reproductive cells, i.e. sperm and egg cells.

�When the sperm and the egg come together to make a Zygote, this is now a Diploid cell.

4 HAPLOID

CELLS

2 DIPLOID

CELLS

What is Heredity?

�Biological phenomenon where traits are passed within a family from one generation to another.��PhenotypePhenotype: the trait, e.g. eye color, height, blood type

��GenotypeGenotype: specific gene or gene combination that causes the trait; one allele from mother, one allele from father.father.��AlleleAllele: different variations of same gene.

��HomozygoteHomozygote: Both alleles are the same allele

��HeterozygoteHeterozygote: Both alleles are different alleles

�Half the genes come from mother; the other half come from father

�Discovered by Gregor MendelGregor Mendel, doing experiments on pea plants (Mendelian inheritance)

What is Heredity? (cont.)

�Researchers look for patterns of inheritance to characterize diseases.

��Four typesFour types:

(1) SporadicSporadic: occurs by itself without an obvious inherited component

(2) DominantDominant: one bad copy causes disease

(3) RecessiveRecessive: two bad copies cause disease

(4) XX--linkedlinked: one bad copy of X chromosome causes disease (red-green color blindness; hemophilia)

Dominant Inheritance

Widows Peak

�The term comes from English folklore, where it was believed that this hair formation was a sign of a woman who would outlive her husband.

Recessive Inheritance

Hitchhiker’s Thumb

�Regular Thumb Hitchhikers Thumb

Attached earlobe --- polygenic

inheritance ??

How do I draw a pedigree?

�Squares are MALES; Circles are FEMALES

�Filled in circles or squares are AFFECTED

�Not filled in circles are UNAFFECTED�Not filled in circles are UNAFFECTED

�Line through circle or square is deceased

Mating

Parents and

Children

(boy child is

older)

Jill’s family-eye color and height

� Jill-brown eyes and 5’9’’

�Brother-brown eyes and 6’2’’

�Mother-blue/green eyes and 5’7’’

�Father-brown eyes and 6’2’’

�Grandmother (mother’s side)-brown eyes and 5’6’’

�Grandfather (mother’s side)-blue eyes and 5’10’’

�Grandmother (father’s side)-brown eyes and 5’3’’

�Grandfather (father’s side)-hazel eyes and 5’11’’

Jill’s Pedigree

HAZ

5’11’’

BRBLBR

5’6’’5’10’’5’3’’

BR=brown eyes; BL=blue eyes; HAZ=hazel eyes; BLGR=Blue/green eyes

BLGRBR

BR BR

5’9’’

5’7’’6’2’’

6’2’’JILL

Description of Hands-On Activity

1. Students each receive a copy of the grid shown below and take it home to collect as much of the information as possible about the following traits: height, attached earlobe, widow’s peak, and hitchhiker’s thumb. Information will be obtained for the student, each of his/her brothers and sisters (full siblings), his/her parents, maternal grandparents and paternal grandparents. Aunts, uncles and other relatives are not necessary for this activity. Students who are adopted or who have little information on their families can use a friend’s grid or be given a sample grid with fictional information.

2. Students will return with the completed grids and use the information on the grid to construct a

pedigree. Each student should receive about 10 circles and 10 squares (templates included below) to represent females and males, respectively. On each shape, students will write the relative’s name, height, and either yes or no after each of the traits. They will glue the shapes to a 14” x 22” piece of poster board in the horizontal orientation with the grandparents’ generation at the top, parents’ generation in the middle, and student/siblings at the bottom. Horizontal lines will be drawn between males and females who mated regardless of marital status and then vertical lines between parents and children. Twins will have a vertical line that divides into a horizontal line with two more vertical segments (see example below).

3. Students will then discuss the patterns of the traits in small groups to decide which appear to be recessive, dominant, or polygenic. Height and attached earlobe are polygenic, widow’s peak is dominant, and hitchhikers thumb is recessive inheritance.

4. The teacher can then start a discussion about each trait and examine a sample student pedigree to show what a dominant, recessive, and polygenic pattern each look like. The teacher can go over the basics of phenotype and genotype, and, using ‘A’ for dominant and ‘a’ for recessive, use the example pedigree to demonstrate the genotype of each person represented on the pedigree. This discussion helps the students to learn to think backwards through the pedigree to determine whether a parent or grandparent is a carrier of a recessive gene.

Pages that follow have sample table for homework and data collection, sample blue squares for males and pink circles for females and a sample pedigree.

Mary

5’ 7”

Hitchhiker’s thumb:

No

Widow’s peak: No

Attached earlobe:

Yes

Height? Hitchhiker’s Thumb?

Widows Peak?

Attached Earlobe

Feet Inches

MOM

DAD

Sister 1

Sister 2

Sister 3

Sister 4

Brother 1

Brother 2

Brother 3

Brother 4

Grandmother (MOMs side)

Grandfather (MOMs side)

Grandmother (DADs side)

Grandfather (DADs side)

SAMPLE PEDIGREE

Maternal

Grandma

Paternal

Grandma

Student’s

Sister

(Twin)

Student

Mother

Maternal

Grandfather

Student’s

Brother

(Twin)

Father

Paternal

Grandpa

FINAL ASSESSMENT

Bernadette did the pre-assessment, showed the PowerPoint slides, and assigned the homework for hands-on activity with her class. The hands-on activity was then done with Jill and a medical student working with Jill in Bernadette’s classroom. The post-assessment was done by Bernadette one day after hands-on activity. Jill and Bernadette then met the following week to discuss the pre- and post-assessment results. There were 18 total students in the freshman/sophomore year biology class. Students were engaged and enjoyed seeing “their pedigrees come to life”. There was a nice class discussion about recessive versus dominant traits that was initiated by looking at their own pedigrees and following the traits of interest through their pedigrees. Feedback received from the students about the lesson and activity was all positive. The results from the pre- and post- assessment are shown in the table below (18 total students). These results show that the students were able to learn a great deal from the lesson and hands-on activity particularly related to pedigrees (0% to 100% for both questions related to pedigrees).

Question # correct answers from pre-assessment (% total)

# correct answers from post-assessment (% total)

(1) What is a gene? 13 (72%) 17 (94%)

(2) Where do you get your genes from?

17 (94%) 18 (100%)

(3) Is every disease caused by your genes?

15 (83%) 16 (89%)

(4) What is a pedigree? 0 (0%) 18 (100%)

(5) Why is a pedigree useful?

0 (0%) 18 (100%)

Jill and Bernadette plan to continue their working relationship and have Jill come to do the hands-on activity with multiple of Bernadette’s classes once a year before state exams.