Making Sense of Genetics

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Making Sense of Genetics

• South Birmingham VTS
• 2007

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True/False

• Genetics is a risk factor for cervical cancer
• Family colorectal cancers are inherited in an
  autosomal dominant manner
• Most mitochondrial genetic disorders manifest
  themselves as myopathies
• The lifetime risk of VTE in someone with a factor
  V Leiden mutation is around 30-40

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Genetics - EMQ

• A) Autosomal dominant (no triplet repeat)
• B) Autosomal dominant (with triplet repeat)
• C) Autosomal recessive
• D) Chromosomal
• E) Mitochondrial
• F) Non-genetic
• G) X-linked dominant
• H) X-linked recessive

• Duchenne MD
• Tuberous sclerosis
• Neurofibratosis Ty 1
• Myotonic dystrophy
• Ovarian agenesis
• Haemophilia B
• Wilsons Disease
• Sturge-Weber
• Phenylkenonuria

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Aims

• Whats it all about?
• Making sense of inheritance
• Taking a Family History
• Red Flags when it should hit you?
• When should we use the tests?
• That dirty word screening
• EBM in genetics
• Cases to discuss

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Overview

• Sickle Cell DM Chicken
  Pox
• Downs CHD Lung
  Cancer
• Single Multifactorial Mainly
• Gene XXXXXXX enviroment

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Making Sense of Inheritance

• Single Gene Disorders
• One copy needed (Autosomal dominant)
• Two copies (Autosomal recessive)
• Sex chromosome (X-linked)
• Chromosomal Disorders

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Autosomal Dominant
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Autosomal Recessive
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X-linked recessive
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Chromosomal

• Downs
• Klinefelters
• 47XXY or XXY syndrome is a condition caused by a
  chromosome nondisjunction in males affected
  individuals have a pair of X sex chromosomes
  instead of just one and are at additional risk
  for some medical conditions. It is named after
  Dr. Harry Klinefelter, a medical researcher at
  Massachusetts General Hospital, who first
  described this condition in 1942. The condition
  exists in roughly 1 out of every 500 males.
• Deletion syndromes
• Chromosome 15q partial deletion is an extremely
  rare genetic disorder, caused by a chromosomal
  aberration in which one of the long ("q") arms of
  human chromosome 15 is deleted.
• If the mother's copy of the chromosomal arm is
  deleted, Angelman syndrome results. If the
  father's copy of the chromosomal arm is deleted,
  Prader-Willi syndrome results.

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Taking a FH - screen

• "Do you have any (some) concerns about diseases
  or conditions that seem to run in the family?
• "Have there been any problems with pregnancy,
  infertility or birth defects in your family?"
• "Have any members of your family died or become
  sick at an early age?"
• "How would you describe your ethnicity?" or
  "Where were your grandparents born?"
• "Are there any other risk factors or non-medical
  conditions that run in your family?"

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Family Medical History       
                                                  
                                                  
                                                  
                                                  
                                                  
                                                  
                                                  
                                                  
                
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Red Flags - when it should hit you?

• When it is obvious!
• Many affected members in different generations
• Strange situations, male breast cancer, bilateral
  tumours.
• Odd tumours (medullary thyroid, phaeo, most
  childhood malignancies)
• Developmental delay, more than one congenital
  abnormality, recurrent miscarriage

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When should we use the tests?
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That dirty word screening

• What are newborn babies screened for?
• In the UK all babies are screened for
  phenylketonuria (PKU) and congenital
  hypothyroidism (CHT). In some areas babies are
  also screened for cystic fibrosis, sickle cell
  disorders and some other conditions.

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EBM in genetics - its difficult

• Prevalence.
• Many genetic diseases are rare and, as a result,
  difficult to study.
• Genotype-phenotype correlation.
• The correlation between a person's genotype (the
  specific variant(s) present in a gene) and
  phenotype (the clinical manifestations) is not
  always predictable.
• Genetic test characteristics.
• Genetic tests may use DNA-based technology to
  assess genotype, or may use other laboratory
  techniques to identify findings indicating an
  inherited condition. Their clinical use is
  limited by their sensitivity/specificity, you
  know all about this!.
• Outcomes.
• Information about the outcome of treatment for
  genetic diseases is often limited, and RCTs are
  often not feasible. For many genetic conditions,
  treatment options are limited or absent. For
  these conditions, testing may be used primarily
  to confirm a diagnosis or provide genetic risk
  information to family members.

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Your turn!