Title: Introduction to Genetics
1Introduction to Genetics
- Bernadette Modell
- UCL Centre for Health Informatics and
Multiprofessional Education (CHIME)
2Challenges 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
3Genetic themes in primary care
- Risk identification
- Risk management
- prevention
4Genetic themes in primary care
Family history Screening Personal risk
Reproductive risk Risk to other relatives
5GP surveys have shown
- Appreciation of the growing importance of
genetics in medicine - Lack of genetic knowledge
- Lack of confidence
6GP 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)
7UK population age distribution, 1991
genetic influences on health
8Practical 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.
9Practical 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
10Annual conceptions of screenable disorders per
10,000 residents (by Strategic HA)
11Carriers, who need to know their carrier status,
per 10,000 residents (by Strategic HA)
12Requests for screening for Hb disorders from 86
practices round Whittington hospital,1995
13Requests for screening for Hb disorders from 5
practices near Whittington hospital,1995-8
14Challenges 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
15Primary care needs
- Knowledge basic genetics
- Skills genetic family history
- Attitudes non-directive counselling
16Primary care needs
- Knowledge basic genetics
- Skills genetic family history
- Attitudes non-directive counselling
- Tools genetic information resources
17Knowledge
18DNA sequencing the human genome? 20-30,000
genes ?
19Types of DNA
20Many 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)
21Some 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
22Genetic (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
23Gene variants all follow the same inheritance
pattern (some exceptions)
24Gene variants all follow the same inheritance
pattern (some exceptions)
25Types 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 ...
26Genetic diagnosis
DNA
metabolite
protein
Blood gp ABO, RhG6PD deficiencyHb variantApo E
1-4
bilirubinphenylalaninecholesterolhomocysteine
27Genetic diagnosis
DNA
metabolite
protein
Blood gp ABO, RhG6PD deficiencyHb variantApo E
1-4
bilirubinphenylalaninecholesterolhomocysteine
haemochromatosisMTHFRcystic fibrosisfamilial
hyper-cholesterolaemia (FH)
28Skills
29The 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
30Extendedfamily
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
31Extendedfamily
Nuclear family
GP, with any patient
A genetic family history can identify risk by
locating relatives with relevant disorders
32Family 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
33Different approaches from specialist and PHC
perspectives
CF
34Per cent of children with 1st cousin parents
35Instrument 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
36A 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
37D 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
38D 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
39D 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
4012/03/2002
D stroke 60
D stroke 61
D Ca ovary
hypertension
50
D Ca ovary 48
Manic depressive
4112/03/2002
D stroke 60
D stroke 61
D Ca ovary
hypertension
50
D Ca ovary 48
Manic depressive
4212/03/2002
D stroke 60
D stroke 61
D Ca ovary
hypertension
50
D Ca ovary 48
Manic depressive
4312/03/2002
D stroke 60
D stroke 61
D Ca ovary
hypertension
50
D Ca ovary 48
Manic depressive
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4888
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
4988
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
5088
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
51Family history, 66 new GP patients
52Categories of risk, 66 new patients
53GP actions indicated
54Genetics 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
55Genetics 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
56In 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
57Wish 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