VARIANTSfor my Daughter’s 4th grade class

Who is this presentation for?

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My background

• BS Geology SUU• CODIS ABI lab ~ 2 yrs• Data Review ~ 5 yrs• QA ~ 2 yrs• Informatics ~ 5 yrs

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WHAT IS DNA?

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Cells

Cells

https://www.youtube.com/watch?v=5VefaI0LrgE

WHAT ARE THE PARTS OF A GENE?

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• Book - Genome– Harry Potter and the Prisoner of Azkaban

• Chapter - Chromosome – Talons and Tea Leaves

• Paragraph - Genes

She stopped again, and then said, in a very matter-of-fact tone, “You look in excellent health to me, Potter, so you'll excuse me if I don't let you off homework today. I assure you that if you die, you need not hand it in.”

~ Professor McGonagall, Harry Potter and the Prisoner of Azkaban

• Sentence - Exon• Word - Amino Acid– die

• Letter - Base (nucleotide)– d

DNA is different from a book

• Bases (letters) – ATCG

• Amino Acids (words) – 21 total

• Always 3 bases long (codon)– ATG – methionine – start codon– CTA – leucine– TAA – Stop codon (TAG, TGA)

Parts of a gene

Parts of a gene

She stopped again, and then said, in a very matter-of-fact tone, “You look in excellent health to me, Potter, so you'll excuse me if I don't let you off homework today. at work must joke if hop last here I assure you that if you die, you need not hand it in.”

Parts of a gene

She stopped again, and then said, in a very matter-of-fact tone, “You look in excellent health to me, Potter, so you'll excuse me if I don't let you off homework today. at work must joke if hop last here I assure you that if you die, you need not hand it in.”

WHAT IS A VARIANT?

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Wild Type

• I assure you that if you die, you need not hand it in.

• Je vous assure que si vous mourez, vous n'avez pas besoin de vous le remettre.

Types of Variants

• Sequence (Seq)• Large Rearrangement (LR)

Types of Variants

• Sequence (Seq)– SNP (Single Nucleotide Polymorphsim)

Types of VariantsI assure you that if you die you need not hand it in.I assure you that if you dye you need not hand it in.SilentI assure you that if you dig you need not hand it in.MissenseI assure you that if you di. NonsenseI assure you that if you din eed noth .DeletionI assure you that if you die xyo unee dno than di ti n. InsertionI assure you that if you cro aky oun eedn oth andi ti n. Indel

Types of Variants

• Large Rearrangement (LR)

Nomenclature

• BIC (Breast Cancer Information Core) • HGVS (Human Genome Variation Society)

Nomenclature

I assure you that if you dig you need not hand it in.

• BIC D40I (156E>G)• HGVS c.156E>G (p.Die40Dig)

154 155 156

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NomenclatureI assure you that if you din eed noth .

• BIC 156del4• HGVS c.156_159del (p.Die40Dinfs*3)

154 155 156

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WHAT IS VARIANT CLASSIFICATION?

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Functional Category

• Will the protein still function?– Deleterious– Suspected Deleterious– Uncertain– Favor Polymorphism– Polymorphism

Clinical Category

• Should you take action?– High Risk – Elevated Risk– Risk May Be Increased– Clinical Significance Unknown– Special Interpretation– Clinically Insignificant

HOW DO VARIANTS CAUSE CANCER?

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Cancer

• Uncontrolled division of abnormal cells.

Gene functions

• Activates enzymes to repair DNA – ATM

• DNA Repair – BRCA1/BRCA2

• Instructs cells to stop dividing – TP53

Gene functions and cancer

• Many mutations in lots of different genes cause cancer

REPORTING VARIANTS

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Legacy Reporting

NGReporting

NGReporting

NGReporting

Resources

http://research.nhgri.nih.gov/bic/http://ghr.nlm.nih.gov/http://www.mayoclinic.org/diseases-conditions/cancer/basics/causes/con-20032378

Image Resourcesbiosocialmethods.isr.umich.eduharrypotter.wikia.comwww.polyvore.comwww.fanpop.comwastedtimefilm.blogspot.comfavim.comwww.cell.comwww.slideshare.netwww.hp-lexicon.orgwww.theage.com.au

www.nature.comwww.themarysue.comblog.bookbaby.combiology.stackexchange.comopshopqueen.wordpress.comhttp://jvanaarsen.weebly.comwww.studyblue.comwww.hp-lexicon.orgwww.technocrates.orgkids.britannica.comwww.cincinnatichildrens.org

THANK YOU.