Introduction to Genetics, with a Focus on Human Genetics

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Introduction to Genetics,with a Focus on Human
Genetics
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Mendels Pea Plants
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Genetics Terms

• Gene and Alleles
• Homozygous
• Heterozygous
• Genotype
• Phenotype
• Dominant
• Recessive

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Homologous Chromosomes vs. Sister Chromatids
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• Gene section of DNA that codes for a protein
• Alleles different molecular versions of a given
  gene (trait)
• Found at the same location (locus) on homologous
  chromosomes
• Homozygous alleles for a given gene (trait) are
  the same
• Heterozygous alleles for a given gene (trait)
  are different

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• Genotype genetic makeup of an organism
• A pea plant is homozygous white.
• Phenotype physical expression of the genotype
• The pea plants flowers are white.

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• Dominant allele the version of the trait that
  is expressed in a heterozygous individual
• Recessive allele - the version of the trait that
  doesnt impact the phenotype in a heterozygous
  individual
• only expressed in an individual who is homozygous
  for the allele

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Writing Genotypes

• A given trait is assigned a letter.
• The dominant version of a trait is shown as the
  upper-case version of the letter.
• The recessive version of the trait is shown in
  lower-case.
• Pick letters that look different upper and
  lower-case!

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• My genotype for eye color Bb
• letter code brown eyes (B), blue eyes (b)
• My phenotype I have brown eyes.
• Which is version of the trait is dominant?
• Am I heterozygous of homozygous for eye color?

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• Our focus will be on single gene disorders
• A defect in a single gene results in the
  disorder.
• Other genetic disorders are chromosomal
  disorders.
• Extra chromosomal material or missing chromosomal
  material results in the disorder
• Karyotype analysis usually shows this type of
  genetic disorder.
• Downs syndrome and cri du chat are examples of
  chromosomal disorders.

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Karypotype for female with Down Syndrome Down
Syndrome results from trisomy at chromosome 21.
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Mothers Karyotype
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Sons Karyotype Cri duChat
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Chromosomes and Gender

• The first 22 pairs of chromosomes are called the
  autosomal chromosomes
• The sex chromosomes determine gender.
• - Human females have two X chromosomes. -
  Males have one X and one Y chromosome.

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Single Gene Autosomal Disorders

• Autosomal traits the genetic information for
  the trait is found on chromosome 1-22, not on one
  of the sex chromosomes
• Autosomal disorders may be
• Recessive
• Co-dominant blood type
• Dominant

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Writing Pedigrees

• Create a pedigree for the family described and
  determine the genotypes of as many individuals as
  possible.
• Father brown eyes, mother blue eyes
• Children
• Daughter brown eyes, married to blue eyed man
• Daughter brown eyes, married to brown eyed man
  two boys have brown eyes
• Son blue eyes, married to blue eyed woman

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Pedigrees

• Circle female
• Square male
• .see board and links below
• http//njaes.rutgers.edu/healthfinance/pdfs/family
  -medical-tree.pdf
• http//www.dnalc.org/view/15990-Making-a-pedigree.
  html

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Autosomal Recessive Inheritance

• Either parent can carry the recessive allele on
  an autosomal chromosome.
• Heterozygotes are symptom-free homozygotes have
  the disorder.
• Two heterozygous parents have a 25 percent chance
  of producing a child with the disorder.
• When both parents are homozygous, all children
  can be affected.

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Autosomal Recessive - Cystic FibrosisSara
Elizabeth
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Co-Dominance

• More than 2 alleles for a given trait
• Some versions of the gene are dominant over
  others
• But they are not dominant over all of the alleles
  
• Both dominant alleles are expressed in
  heterozygotes

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Writing Blood Type Alleles2 methods

• There are 3 alleles for blood type A, B, O
• A (IA ) and B (IB ) are co-dominant
• Both A and B are dominant over the allele for O
  (i) blood
• Writing alleles for blood type
• A IA
• B IB
• O i

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Blood Types and Genotypes

• Type A Blood

A
A
A
O
heterozygous IA i
homozygous IA IA
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Blood Types and Genotypes

• Type B Blood

O
heterozygous IB i
homozygous IB IB
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Blood Types and Genotypes

• Type AB Blood
• Type O Blood

IA IB
O
O
i i
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Genetics

• Dominant disorders the allele for the disorder
  is dominant and the healthy version of the trait
  is recessive
• The genetic form of Huntingtons disease is
  dominant to being healthy.
• Some forms of breast cancer are dominant
• More to come on this

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Sex-linked Traits

• X-linked traits genetic information for the
  trait is located on the X chromosome
• no genetic info about the trait on the Y chromo
• Examples Hemophilia, color blindness, Duschenne
  muscular dystrophy
• Y-linked traits (not many known)
• Allele for hairy ears is Y-linked

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Genetics and Breast and Ovarian Cancer

• An Introduction

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Genetics and Breast Cancer

• An inherited form of breast/ovarian cancer is an
  autosomal dominant condition
• Occurs as a result of mutations in BRCA1 or BRCA2
  genes
• BRCA 1 - gene on chromosome 17
• BRCA 2 - gene on chromosome 13

BRCA 2 Chromosome 13
BRCA 1 Chromosome 17
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Function BRCA Genes

• The BRCA genes seem to code for tumor suppressor
  proteins
• Needed to keep cells from becoming cancerous
• BRCA gene products also play a role in
• DNA repair
• Cell Cycle control
• And other functions

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Heterozygous Individuals

• Theoretically, most individuals with the BRCA 1
  or 2 gene will also carry a normal allele on the
  other paired chromosome.
• Normal allele should make functional BRCA protein
  and it should act as a tumor suppressor.

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Heterozygous Individuals

• HOWEVER..
• In most breast and ovarian cancers studied in
  those carrying the mutation the normal allele is
  deleted or loses function, resulting in loss of
  all function of the BRCA 1 or 2 proteins.
• http//www.youtube.com/watch?vC503LJrUGKc

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BRCA1 BRCA2

• Over 2000 different mutations have been
  identified in the BRCA genes
• Most BRCA1 and BRCA2 mutations are predicted to
  produce a truncated protein product, and a loss
  of protein function.
• Not all have the same cancer risk
• The cancer risk associated with each mutation
  depends on the impact of the mutation on the
  proteins structure and function.

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Incidence of BRCA genes

• BRCA1
• 3.5 Hispanic,
• 1.3 to 1.4 African American,
• 0.5 Asian American,
• 2.2 to 2.9 non-Ashkenazi Caucasian, and
• 8.3 to 10.2 Ashkenazi Jewish.
• BRCA2
• 2.6 African American and
• 2.1 Caucasian

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Increased Risk of Cancer

• Individuals with one copy of either mutated gene
  (BRCA1 and BRCA2) are at increased risk of breast
  and/or ovarian cancer.
• 60 lifetime risk breast cancer
• 10-40 lifetime risk ovarian cancer

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Alexandra Bests Story

• Alexandra Bests mother and grandmother died from
  breast cancer.
• After visiting the doctor to voice her concerns,
  she discovered that researchers had traced the
  origins of her family's history of breast cancer
  back to three Italian brothers who emigrated to
  England in the 1850s.
• Thirty-one members of her family had developed
  the disease since then - and the researchers said
  she was likely to be carrying the gene.

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Alexandras Relatives many generations back
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What she did.

• Alexandra was tested for the BRCA gene and found
  to carry it.
• She decided to have a preventative mastectomy
• During preparation for the operation a cancerous
  lump was found in her breast.
• Lead to chemotherapy after a double mastectomy.

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• Alexandras extended family was tested and 11
  were found to carry the BRCA gene
• 8 have had preventative surgery

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Family positive for BRCA 1 deleterious mutation

positive for mutation Preventive measure
taken


Ethel E. Laird Breast 28 Death 32

Marjorie Halt Ovarian 64,69 Death 69
Maryann Laird Breast 44, 46 Ovarian 63 Death 64
Paula (59) Breast 48
Barbara Breast 38, 40 Death 44
Susan Halt Davis (53) Breast 49


Linda Halt Nicholson (60)
Steve Halt (57)

BRCA I Neg Julianne
BRCA I Neg Kevin (32) 2 Children
Jeffrey (40) No Children
Gina (30)
Kristi (28)
Amber (28)
Richard Death 3-5-07 Age 25 Car accident
Jennifer, 22
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