Introduction to Genetics

1
Introduction to Genetics

• Bernadette Modell
• UCL Centre for Health Informatics and
  Multiprofessional Education (CHIME)

2
Challenges for genetics in primary care

• Attract interest and involvement
• Adjust focus from individual to family
• Cope with diversity
• of risks (conditions, groups, prevalences)
• of GPs and practices
• of families and kinship patterns

3
Genetic themes in primary care

• Risk identification
• Risk management
• prevention

4
Genetic themes in primary care
Family history Screening Personal risk
Reproductive risk Risk to other relatives
5
GP surveys have shown

• Appreciation of the growing importance of
  genetics in medicine
• Lack of genetic knowledge
• Lack of confidence

6
GP surveys have shown

• Appreciation of the growing importance of
  genetics in medicine
• Lack of genetic knowledge
• Lack of confidence
• Interest in the family history
• No interest in screening
• Little interest in reproductive risk
• In Addressing Genetics Delivering Health
  (Hilary Burton, Cambridge Public Health Genetics
  Unit)

7
UK population age distribution, 1991
genetic influences on health
8
Practical drivers of genetic approaches in
primary care

• Inclusion of the family history in national
  service frameworks (NSFs) for diabetes and
  cardiovascular disease
• how to take it is not specified
• the literature supports the family history as a
  risk factor, but diverse (and usually limited)
  methods were used.

9
Practical drivers of genetic approaches in
primary care

• National Screening Committee (NSC) funding of
  first genetic education programme for primary
  care
• generic genetic education (PEGASUS) - arising
  from national screening programme for sickle cell
  and thalassaemia (lead Joe Kai, Derby)
• informed choice - arising from Downs syndrome
  screening

10
Annual conceptions of screenable disorders per
10,000 residents (by Strategic HA)
11
Carriers, who need to know their carrier status,
per 10,000 residents (by Strategic HA)
12
Requests for screening for Hb disorders from 86
practices round Whittington hospital,1995
13
Requests for screening for Hb disorders from 5
practices near Whittington hospital,1995-8
14
Challenges for genetics in primary care

• Attract interest and involvement
• Adjust focus from individual to family
• Cope with diversity
• of risks (conditions, groups, prevalences)
• of GPs and practices
• of families and kinship patterns

15
Primary care needs

• Knowledge basic genetics
• Skills genetic family history
• Attitudes non-directive counselling

16
Primary care needs

• Knowledge basic genetics
• Skills genetic family history
• Attitudes non-directive counselling
• Tools genetic information resources

17
Knowledge
18
DNA sequencing the human genome? 20-30,000
genes ?
19
Types of DNA
20
Many coding sequences are highly conserved

• Many proteins have only one form, and the DNA and
  protein sequence is the same in most people.
• This indicates that every detail of the protein
  structure is essential for its function.
• A mutation in the coding sequence of such genes
  often has a strong effect - causes a single gene
  disorder.
• Such mutations are rapidly lost (selected out)

21
Some proteins tolerate considerable variation,
with little effect on function

• Such proteins are polymorphic - have a range of
  common variants
• e.g. blood groups, apoliprotein E, HLA
• People can have a combination of any two
  polymorphic variants
• Inherited differences between people reflect
  inheritance of many different polymorphisms

22
Genetic (protein) polymorphisms

• Most have little obvious effect on health
• Some contribute to multifactorial disorders
• Polygenic effects particular genetic
  combinations increase risk of e.g. cardiovascular
  disease, diabetes, stroke, dementia
• Environmental effects particular genetic
  combinations are useful in one environment but
  increase risk in another, e.g risk of
  cardiovascular disease and diabetes in some
  ethnic groups

23
Gene variants all follow the same inheritance
pattern (some exceptions)
24
Gene variants all follow the same inheritance
pattern (some exceptions)
25
Types of genetic influence on health

• Single gene disorders -
• rare metabolic diseases,
• familial cancers
• Genetic predisposition to
• cardiovascular disease
• diabetes
• atopy ...
• Response to environmental influences
• drug resistance and susceptibility
• effects of diet ...

26
Genetic diagnosis
DNA
metabolite
protein
Blood gp ABO, RhG6PD deficiencyHb variantApo E
1-4
bilirubinphenylalaninecholesterolhomocysteine
27
Genetic diagnosis
DNA
metabolite
protein
Blood gp ABO, RhG6PD deficiencyHb variantApo E
1-4
bilirubinphenylalaninecholesterolhomocysteine
haemochromatosisMTHFRcystic fibrosisfamilial
hyper-cholesterolaemia (FH)
28
Skills
29
The family history in primary care

• A standard part of the medical history
• Psychosocial functions - peoples relationships
  with each other
• Genetic functions - peoples relationships to
  each other

30
Extendedfamily
Nuclear family
Affected person
Specialist - clinical geneticistpaediatrician,
cardiologist
A known diagnosisthe aim of family studies is
to identify relatives with, or without, a
specific variant
31
Extendedfamily
Nuclear family
GP, with any patient
A genetic family history can identify risk by
locating relatives with relevant disorders
32
Family history a pincer movement on families
Extendedfamily
Nuclear family
Specialist - clinical geneticistpaediatrician,
cardiologist
GP, with any patient
A genetic family history can identify risk by
locating relatives with relevant disorders
A known diagnosisthe aim of family studies is
to identify relatives with, or without, a
specific variant
33
Different approaches from specialist and PHC
perspectives
CF
34
Per cent of children with 1st cousin parents
35
Instrument for taking a primary care family
history (Dr Nadeem Qureshi)

• Simple question(s) (with/without prompt sheet)
• Self-administered questionnaire (with prompt
  sheet)
• Pedigree questionnaire

36
A study of the genetic element in the GP family
history (Nadeem Qureshi Co)

• New patients registering with six local practices
• Completed a simple family history questionnaire
• Had a structured interview with the researcher,
  to construct a full family tree

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D Ca bowel 48
D blood clot 91




67
72
59
Ca bowel 42
CoD not noted













41
43
44
49
57
46
43
Ca cervix 43
D cot death
D accident







Int polyp removed 40



















4
18
15









38
D Ca bowel 48
D blood clot 91




67
72
59
Ca bowel 42
CoD not noted













41
43
44
49
57
46
43
Ca cervix 43
D cot death
D accident







Int polyp removed 40


















4
18
15









39
D Ca bowel 48
D blood clot 91




67
72
59
Ca bowel 42
CoD not noted













41
43
44
49
57
46
43
Ca cervix 43
D cot death
D accident







Int polyp removed 40


















4
18
15









40
12/03/2002
D stroke 60

D stroke 61
D Ca ovary
hypertension

50
D Ca ovary 48

Manic depressive

41
12/03/2002
D stroke 60

D stroke 61
D Ca ovary
hypertension
50
D Ca ovary 48

Manic depressive

42
12/03/2002
D stroke 60

D stroke 61
D Ca ovary
hypertension
50
D Ca ovary 48

Manic depressive

43
12/03/2002
D stroke 60

D stroke 61
D Ca ovary
hypertension
50
D Ca ovary 48

Manic depressive

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88
Heart attack 60
Old age 70
Cancer 60
Cancer 70
old age 80
old age 80
Committed
Committed

Old age 80





Arrythmia 85

suicide 20
suicide 20












69
64
Committed


Arrythmia 68
Thalassemia
suicide 25
carrier

Hysterectomy 40

38
40


Thalassemia
endometriosis

carrier

49
88
Heart attack 60
Old age 70
Cancer 60
Cancer 70
old age 80
old age 80
Committed
Committed

Old age 80





Arrythmia 85

suicide 20
suicide 20












64
69
Committed


Arrythmia 68
Thalassemia
suicide 25
carrier

Hysterectomy 40

38
40


Thalassemia
endometriosis

carrier

50
88
Heart attack 60
Old age 70
Cancer 60
Cancer 70
old age 80
old age 80
Committed
Committed

Old age 80





Arrythmia 85

suicide 20
suicide 20












64
69
Committed


Arrythmia 68
Thalassemia
suicide 25
carrier

Hysterectomy 40

38
40


Thalassemia
endometriosis

carrier

51
Family history, 66 new GP patients
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Categories of risk, 66 new patients
53
GP actions indicated
54
Genetics in primary care

• Because a family history is part of the basic
  medical history, there is already a lot of
  genetics in primary care. It needs to be made
  explicit.
• When a GP recognises risk, this affects the way
  they manage the patient
• Unless GPs recognise risk, patients will not get
  the preventive care they need

55
Genetics in primary care

• A family tree is the best way to present family
  information for pattern, and risk, recognition
• We need cost- and time- efficient methods for
  eliciting, recording and presenting the genetic
  element in the primary care family history

56
In genetics

• Information is the key therapeutic intervention
• There are always three necessary information
  paths
• about risk to the person themselves
• about risk to their children
• about risk to other relatives

57
Wish list for the next 5 years

• Primary care genetic education programme
• Standard tools for taking, recording and updating
  family trees
• Electronic, accessible, diagnosis-specific
  information for patients and primary care
  teams(web-based electronic records)
• Support of community-based genetic counsellors
• Community (industrial scale) genetic diagnosis
  laboratories