A clinical approach to genetic testing for non-specialistsBMJ 2017; 358 doi: https://doi.org/10.1136/bmj.j4101 (Published 28 September 2017) Cite this as: BMJ 2017;358:j4101
All rapid responses
Reading the response of Prof Konotey-Ahulu I am struck by the incompetent use of scientific terminology by too many people who ought to know better.
These ladies and gentleme , caring for people with haemoglobin varients, normal and abnormal, need a lexicon. Prepared by established experts like Alison Streetly and Konotey-Ahulu. They will need a series of sessions to practise ............HOW TO.?
We may then hope for a better care for the persons who are advised to undergo the tests.
Competing interests: No competing interests
Commenting on the instructive PRACTICE article of Semsarian and Ingles  Allison Streetly was right to point out that genetic testing “is not solely the terrain of those who run DNA testing services”.  Specialists majoring on DNA testing and Genome sequencing are often surprised to learn that remarkable genetic information on beta-globin variant genes can be obtained using simple Sickling Test plus Haemoglobin Electrophoresis.
GREATEST GLOBAL GENETIC BURDEN UNMASKED WITHOUT DNA TESTS
The commonest beta-globin variant genes are qualitative, Haemoglobins S & C, and quantitative, beta-Thalassaemia. Although heterozygotes AS, AC, beta-Thalassaemia Trait are not disease burden [3, 4, 5] they need identification for Counselling. Surprising fact is that one in every three West Africans at home and abroad is heterozygote for Haemoglobin S or C genes [6-33] which means 1 in 9 procreating couples are carriers “AS” or “AC”.
CORRECT DEFINITIONS ARE VITAL FOR GENETIC COUNSELLING
When WHO has laid down correct Terminology [34 35], we find reputable publications/Guidelines riddled with confusion, most glaringly confusing Sickle Cell Trait with Sickle Cell Disease [36-40], and sometimes describing both Trait and Disease phenotypes in same person –  all of which mistakes have been exposed [42-49]. Doyen of Abnormal Haemoglobins Professor Hermann Lehmann FRS wrote to The Times-London  that Sickle Cell Traits had run at Olympic Games at Mexico City 7000 ft and won Gold Medals, yet reports of Sickle Cell Traits dying at 4000ft continued, ensuring Insurance Companies made huge profits. [51 52].
Sickle Cell Trait: One Normal beta haemoglobin gene “A” plus 1 Abnormal haemoglobin gene “S” - phenotype “AS” with “A” greater than “S”. Traits have 3 ranges of “S” haemoglobin 20-28%, 30-35%, and 37-39.7% . Always quantify Haemoglobin S to be sure. When “S” exceeds “A” it is not Trait. 
Sickle Cell Disease: Possession of 2 Abnormal Haemoglobin genes at least one of which is the S gene, thus the phenotypes “SS”, “SC”, “SD”, “S-beta-Thalassaemia”, “SKorle-Bu”,  etc – are Sickle Cell Diseases. Only the “SS” phenotype is “Sickle Cell Anaemia” because anaemia is its main characteristic; also written “Sickle Cell Disease (SS)” to specify both abnormal haemoglobins are the same. [3 4 5 55].
The terms “Sickle Cell Trait” and “Sickle Cell Disease” are, therefore, fixed Genetic Terms which must never be interchanged. The term “Sickle Cell Diseases” which Archives of Internal Medicine invited me to use , unmistakably connotes disease phenotypes, while “Sickle Cell Disorders” is an obfuscation that has wrongly included Traits [46 49]. Disappointingly, both Trait and Disease phenotypes have been described as “Sickle Cell Disorder” in UK [57 58]. How could one with Trait “disorder” win Olympic GOLD at 7000 ft beating the world? When Rachel Thompson writes “Europe Sickle Cell Disorders Market Highlights-2015”, would Sickle Cell Traits who had been told they had a “disorder” not rush to take unwarranted advantage of her “market analysis, competitive landscape, and sickle cell disorders drug sales forecast for Germany, France, Italy, Spain, and UK”? . Even after Graham Serjeant and I demonstrated that Sickle Cell Disease Patients (2 Abnormal genes) could be managed successfully from childhood to university without specific drugs like Hydroxyurea earmarked for that purpose? [3 23 60 61]
Just Wikipediate or Google “Sickle Cell Trait” and you get a mixture of truth and error which latter has led to (i) selective abortion (ii) insurance injustice (iii) social humiliation (iv) sports ban (v) employment exclusion (vi) clinical mismanagement and (vii) coroners’ perversion of truth. Elliott Vischinsky’s assertion about “sickle cell trait”  frightens 20% of West Africans until the wrong science is pointed out. Even the NIH is using the confusing “disorder” terminology. 
SOCIAL MEDIA MISINFORMATION FROM GENETIC TEST RESULTS
When experts get things wrong [36 37 38 39 40] is it surprising that patients who describe themselves as “Sickle Cell Trait” send photos of themselves from hospital beds, or tweet from home claiming severe complications of sickle cell trait? One “Evans BornGreat” told the world on Facebook  that he was suffering from Sickle Cell Trait. I advised him to visit his doctor and ask for “Haemoglobin Electrophoresis with percentages of haemoglobin fractions”. On 13 December last week he sent this message: “I thought I was AS, but the tests show I am SC.” Doctors are writing Sickle Cell Trait as “SCT” which makes disease SC phenotype (2 abnormal genes) be perceived as AS-phenotype. Facebook also grabs the flawed Lancet publication  and runs with it , justifying my protest! 
GENETIC TESTS TO DETECT BOTH DISEASE AND TRAIT FOR COUNSELLING
Allison Streetly’s excellent NHS Sickle Cell and Thalassaemia Programme  would have identified 2-abnormal-genes babies to be followed up. I said in the BMJ 35 years ago that sickle cell disease patients needed identifying before “they are brought to hospital dead from their first sickle cell crisis” . When a Massachusetts Law demanded blood test for “the disease known as sickle cell trait or sickle cell anemia” [67 68] how does meaningful Genetic Counselling begin?
My Genetic Counselling and Voluntary Family Size Limitation (GCVFSL) advice is simplified [69-79]. Normal Haemoglobin gene “A” is “NORM” while Abnormal Haemoglobin gene is “ACHE”. Therefore, my parents who, like 1 in 3 of all Ghanaians, were Trait NORMACHE phenotypes produced 11 children with 3 ACHEACHE (sickle cell disease), 4 NORMACHE Traits, and 4 NORMNORM. I invented 3 different cubes (the kanad: “konotey-ahulu norm ache dice”) to represent Normal, Trait, and Disease male-female phenotypes which can be cast at each other. See www.sicklecell.md  for Home Page kanad video demonstration which is totally different from NIH Approach . Papaa’s NORMACHE against Mamma’s NORMACHE for each pregnancy produced the phenotypes mentioned above . The Genetic Index MPSI that I invented [75 78 79] proves to men their greater responsibility for genetic burden limitation. Polygamous Traits proliferate genes [75 77]. Testing for G6PD Deficiency is also vital for Africans [21 22 80 81 82].
Enquirers determined to avoid disease phenotype offspring have 2 choices: Probability (Genetic Gambling) and Predictability, which latter the kanad gives a 100% correct answer about which mating phenotypes avoid ACHEACHE offspring.
Competing Interest: I come from a Sickle Cell Disease Family: My Trait Parents produced 11 children: 3 disease-phenotype, 4 Traits, 4 with no abnormal Haemoglobin gene . I do not apologize for continuing to teach less knowledgeable people who do not come from a Sickle Cell Disease home.
Felix I D Konotey-Ahulu FGA MB BS MD(Lond) DSc(UCC) FRCP(Lond) FRCP(Glasg) DTMH(L’pool) FGCP FWACP FTWAS ORDER OF THE VOLTA (OFFICER)
Kwegyir Aggrey Distinguished Professor of Human Genetics University of Cape Coast, Ghana; Former Consultant Physician Genetic Counsellor in Sickle Cell and Other Haemoglobinopathies Korle Bu Teaching Hospital & Director Ghana Institute of Clinical Genetics, and 9 Harley Street, Phoenix Hospital Group, London W1G 9AL.
1. Semsarian C, Ingles J. PRACT5ICE: A clinical approach to genetic testing for non-specialists. BMJ 2017; 358 doi: 10.1136/bmj.j4101. 28 Sept. 2017.
2. Streetly A. A common definition of genetic testing – can we agree on one? http://www.bmj.com/content/358/bmj.j4101/rapid-responses BMJ 18 October 2017.
3. Konotey-Ahulu FID. The Sickle Cell Disease Patient: Natural History from a Clinico-epidemiological study of the first 1550 patients of Korle Bu Hospital Sickle Cell Clinic. Macmillan Press Ltd, London 1991 & 1992 and T-A’D Co Ltd Watford 1996
4. Serjeant GR. Sickle Cell Disease. Oxford University Press, Oxford 1992.
5. Weatherall DJ, Clegg JB. The Thalassaemia Syndromes. Blackwell Scientific, Oxford 2008.
6. Edington GM. Sickle cell anaemia in the Accra district of the Gold Coast. Br Med J 1953;2:957 https://doi,org/10.1136/bmj.2.4843.957 October 31 1953
7. Lehmann H. The distribution of the sickle cell trait. J Clin Path 1953; 6: 329.
8. Edington GM. Sickle cell trait and sickle cell anaemia. BMJ 1954.1: 871
9. Edington GM, Lehmann H. A case of sickle cell haemoglobin C disease and survey of haemoglobin C incidence in West Africa. Trans Roy Soc Trop Med Hyg 1954; 48: 332-336.
10. Edington GM, Lehmann H. Expression of the sickle cell gene in Africa. BMJ 1955; 1: 1308-1311.
11. Edington GM, Lehmann H. Expression of the sickle cell gene in Africa. BMJ 1955; 2: 1328.
12. Edington GM and Lehmann H. The distribution of Haemoglobin C in West Africa. Man 1956; 34-36.
13. Edington GM, Laing WN. Relationship between Haemoglobin C and S and malaria in Ghana. BMJ 1957; 2: 143-1456.
14. Lehmann H, Nwokolo C. The River Niger as a barrier in the spread eastwards of Haemoglobin C. A survey of haemoglobins in the Ibo. Nature 1959; 183: 1587-1588.
15. Thompson GR. of Haemoglobins S, & C in Ghana BMJ 1962; 1: 682-685.
16. Thompson GR, Lehmann H. Combinations of high levels of Haemoglobin F with A, S and C in Ghana. BMJ 1962; 1:1521-1523.
17. Thompson GR. Malaria and stress in relation to Haemoglobin S and C. BMJ 1963; 2: 976-978.
18. Edington GM. Abnormal Haemoglobins in West Africa. Ghana Medical J 1963; 2: 83-87.
19. Edington GM, Watson-Williams EJ. Sickling, Haemoglobin C, Glucose-6 Phosphate Dehydrogenase Deficiency and malaria in Western Nigeria. In Abnormal Haemoglobins. Editors Jonxis JHP and Delafresnaye JF. Blackwell Scientific Publications, Oxford 1965, pages 393-401.
20. Lehmann H. Hemoglobinopathies. Abnormal Hemoglobins and Thalassaemias. In Health Problems in Developing States. Editors Prywe SM, Davies A. Grune and Stratton Inc., 1968, pp158-167.
21. Ringelhann B, Dodu SRA, Konotey-Ahulu FID, Lehmann H. A Survey for Haemoglobin Variants, Thalassaemia and Glucose-6-Phosphate Dehydrogenase Deﬁciency in Northern Ghana. Ringelhann B, Dodu SRA, Konotey-Ahulu FID, Lehmann H. Ghana Med J 1968; 7: 120-124. Sept. 1968.
22. Konotey-Ahulu FID. EDITORIAL Hereditary Qualitative and Quantitative Erythrocyte Defects in Ghana: An Historical and Geographical Survey. Ghana Med J 7: 118-119. Sept. 1968
23 Konotey-Ahulu FID and Ringelhann B. Sickle-cell anaemia, sickle-cell thalassaemia, sickle-cell haemoglobin C disease and asymptomatic haemoglobin C thalassaemia in one Ghanaian family. BMJ 1969 Mar 8; 1(5644): 607-612. doi:10.1136/bmj-1.5644/607 March 8 1969 http://www.bmj.com/cgi/reprint/1/5644/607.pd
24. Konotey-Ahulu FID. Patterns of clinical haemoglobinopathy. E Afri Med J 1969 Mar; 46(3): 149-156. PMID: 5800410 [PubMed – indexed for MEDLINE]
25. Ringelhann B, Konotey-Ahulu FID, Yawson G, Bruce-Tagoe AA, Miller A and Huisman THJ. Alpha Thalassaemia in West Africa. Symposium on Medical Genetics 1969, Hungary, page 81.
26. Konotey-Ahulu FID. Pattern of Sickle Cell Disease in Accra - A Study of 1,550 Consecutive Patients: A Thesis Presented 1971 for The Postgraduate Degree Of Medicine (MD) In The University Of London. [Awarded in 1972]
27. Konotey-Ahulu FID. History of Sickle Cell Disease in Africa. Geographical Distribution and Population Dynamics of Haemoglobins S and C with special reference to West Africa. Ghana Med J 1972; 11: 397-412.
28. Lehmann H, Huntsman RG. Man’s Haemoglobins. North-Holland Publishing Company 1974. Amsterdam/
29. Gbedemah KA, Acquaye CTA, Konotey-Ahulu FID and Reindorf CA. Haemoglobin phenotype patterns in more than 1,000 consecutive new-born babies in Ghana. Ghana Med J 1976; 15: 253-256
30. Konotey-Ahulu FID. The spectrum of phenotypic expression of clinical haemoglobinopathy in West Africa. New Istanbul Contribution to Clinical Science 1978 Dec; 12(3-4): 246-257.
31. Bonney GE, Walker M, Gbedemah K and Konotey-Ahulu FID. Multiple births and visible birth defects in 13000 consecutive deliveries in one Ghanaian hospital. In Proceedings of the Second International Congress on Twin Studies Part C Ed Nance W. Progress in Clinical and Biological Research 1978; 24 Pt B: 105-108.
32. Ringelhann B, Konotey-Ahulu FID. Hemoglobinopathies and thalassemias in Mediterranean areas and in West Africa: Historical and other perspectives 1910 to 1997 - A Century Review. Atti dell’Accademia dell Science di Ferrara (Milan) 1998;74: 267-307.
33. Konotey-Ahulu FID. Should we abandon routine blood tests? No, not when hereditary erythrocytopathy poses a real problem in a so-called multiracial population! BMJ Rapid Response [No, do Abnormal Haemoglobin and G6PD tests routinely] www.bmj.com/content/357/bmj.j2091/rr-15
34. Boyo AE, Cabannes R, Conley CL, Lehmann H, Luzzatto L, Milner PF, Ringelhann B, Weatherall DJ, Barrai I, Konotey-Ahulu FID and Motulsky AG. Geneva WHO Scientific Group on Treatment of Haemoglobinopathies and Allied Disorders. (Technical Report) 1972; 509:83 pages.
35. Woodruff AW, et al [Colonial Medical Research Committee Working Party on Sickle Cell Trait and Sickle Cell Anaemia]. Terminology of the hereditary Haemoglobinopathies with haemoglobin variants. BMJ 1957; 1: 1235. www.bmj.com/content/1/5029/1235 //doi.org/10.1136/bmj.1.5029 May 25.
36. Vichinsky Elliott P. Sickle cell trait. Literature Review UpToDate [Accessed 18 Feb 2011] http://www.uptodate.com/contents/sickle-cell-trait?view=print asserts wrongly that “Renal medullary carcinoma is a rare and aggressive tumor that is seen almost exclusively in young patients with sickle cell trait.”
37. Kepron Charis, Somers Gino R, Pollamen Michael S. Sickle Cell Trait Mimicking Multiple Inflicted Injuries in a 5-Year-Old Boy. Journal of Forensic Sciences Volume 54, No.5, pp 1141 t0 1145 September 2009.
38. Key Nigel S, Derebail Vimal K. Sickle Cell Trait: Novel Clinical Significance. Hematology 2010: 418-422. “During exercise, Sickle Cell Trait appears to be a risk factor for sudden death and/rhabdomyolysis, particularly when the exercise is intense, and is performed at high altitude …”
39. Tsaras, G, Owusu-Ansah A, Boateng FO, Amoateng-Adjepong, Y. Complications associated with sickle cell trait: a brief narrative review. American Journal of Medicine 2009; 122(6): 507-512.
40. Rhida A, Khan A, Al-Abayechi S, Puthenveetil V. Acute compartment syndrome secondary to rhabdomyolysis in a sickle cell trait patient. Lancet 2014; 384:2172 [No evidence for Sickle Cell Trait was presented in this Lancet article (See Reference 47)].
41. Witkowska HE, Lubin BH, Beuzard Y et al. Sickle cell disease in a patient with sickle cell trait and compound heterozygosity for haemoglobin S and haemoglobin Quebec-Chori. New England Journal of Medicine 1991; 325: 1150-1154. [Note that the title of this article is incorrect: No human being can be said to have both Sickle cell trait and Sickle Cell Disease. The ‘AS’ pattern is sickle cell trait pattern, but this ‘A’ is not a true ‘A’ but the new haemoglobin called Quebec-Chori, producing a disease phenotype, not trait.]
42. Konotey-Ahulu FID. World Sickle Cell Day 19h June 2014 http://bit.ly/1FuNXPi Beware of symptomatic sickle cell traits. Lancet, Feb 29, 1992, page 555. http://www.thelancet.com/journals/lancet/article/PII0140-6736(92)90377-F/fulltext http://bit.ly/2d18oOL [Re: The enigma of Haemoglobin Quebec-Chori – See Ref. 41]
43. Dyson Simon, Bosswell Gwyneth. Sickle Cell and Deaths in Custody. Whiting and Birch, London: June 2009; 230 pages “The misuse of Sickle Cell Trait to explain away sudden deaths”.
44. Konotey-Ahulu FID. Blaming sudden death on Sickle Cell Trait? Flaws in article of Charis Kepron, Gino Somers and Michael Pollanen [Reference 37 above Exposed]. September 4 2011 www.sicklecell.md/blog/?p=105 or www.konotey-ahulu.com/blog/?p=105
45. Konotey-Ahulu FID. Sickle Cell Trait Misinformation or Disinformation. http://blog.sicklecell.md/sicklecell/sickle-cell-trait-misinformation-an... August 2017
46. Konotey-Ahulu FID. Further Communication on “Sickle Cell Trait Misinformation and Disinformation” and Sickle Cell Terminology: Disease or Disorder? http://blog.sicklecell.md/sicklecell/further-communication-on-sickle-cel...
47. Konotey-Ahulu FID. Dangerously flawed diagnosis of sickle cell trait in compartment syndrome rhabdomyolysis http://bit.ly/2d4t9Zd http://www.sicklecell.md/blog/index.php/2016/09/dangerously-flawed-diagn... [No evidence for Sickle Cell Trait was presented in the Lancet article (Reference 40)].
48. Sickle Cell Trait: As with Statins, when leading editors disagree please give principles same weight as details Sept 27 2016. http://www.sicklecell.md/blog/index.php/2016/09/statins-when-leading-edi... http://bit.ly/2dy5fUJ
49. Konotey-Ahulu FID. Sickle Cell Trait Confusion. Is it Deliberate? Or is This Ignorance? http://blog.sicklecell.md/sicklecell/sickle-cell-trait-confusion-is-it-d... August 2017.
50. Lehmann Hermann. Sickle cell and flying. The Times (London) 4 Jan 1972 That was when the “Science Editor” used a wrong report on “Sickle Cell Trait and Flying” in BMJ to recommend grounding of all Black Air Crew. [See details in:
(a) Green RL, Huntsman RG, Serjeant GR. Sickle cell trait and altitude. Br Med J 1971; 4: 593-595.
(b) Djabanor F F T. Sickle cell trait and altitude. Brit Med J 1972; 1: 113
(c) Addae R O. Sickle cell trait and altitude. BMJ 1972; 1: 53. [10 criteria (Addae’s Criteria) required to satisfy clinicians in regions where 1 in 5 people have the sickle cell trait that symptoms are due to the trait and nothing else.]
(d) Konotey-Ahulu FID. Sickle cell trait and altitude. BMJ 1972; 1: 177-178.
(e) Konotey-Ahulu FID. An international sickle cell crisis. [Editorial] Ghana Medical J; 1972; 11: 4-8 [A detailed account of how BMJ withdrew report]
(f) Konotey-Ahulu FID. Sickle cell trait and altitude. BMJ 1972; 2: 231-32 April 22
(g) Green RL, Huntsman RG, Serjeant GR. Sickle cell and altitude. Brit Med J 1972; 2: 294
51. Konotey-Ahulu FID. Insurance and genetic testing. Lancet 1993, 341: 833. March 27 [See Reference 52 for when Dr Konotey-Ahulu was given 4 Body Guards in Philadelphia for stressing “Sickle Cell Disease is NOT Sickle Cell Trait and vice versa!” and thus upsetting Insurance Companies]
52. Konotey-Ahulu FID. Four bodyguards and the perils of unmasking scientific truths. BMJ 2007; 335: 210-211. www.bmj.com/cgi/content/full/335/7612/210
[Day & Date: Wednesday 31st May 1972 – Philadelphia, Dr Martin Luther King Jr Foundation Award Ceremony for Outstanding Contributions in Sickle Cell Disease: Banquet – Dr Konotey-Ahulu’s Keynote Address was on ‘Difference between Sickle Cell Trait and Sickle Cell Disease’. Those also honoured present on the platform with me included Nobel Prize Winners Linus Pauling and Max Perutz, then Hermann Lehmann, Roland Scott, J V Neel, Bella Ringelhann, A C Allison, James Bowman, Helen Ranney, Charles Whitten, L Diggs, L Conley, Sam Charache & Graham Serjeant].
53. Konotey-Ahulu FID. Alpha-Thalassaemia nomenclature and abnormal haemoglobins Lancet 1984; 1: 1024-25 May 5 [“Of 82 consecutive sickle cell traits seen in London in 24 months 36 (44%) had just one quarter of the total haemoglobin as sickle haemoglobin (mean 25%, range 20-28%). The three known peaks of haemoglobin S proportion in the West African sickle cell sickle cell trait are around 25%, around 30& and around 38%”)
54. Konotey-Ahulu FID, Gallo E, Lehmann H, Ringelhann B. Haemoglobin Korle Bu (alpha2 beta2 73 Aspartic Acid –> Asparagine), showing one of the two amino acid substitutions of Haemoglobin C Harlem. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1468514 J Med Genet 1968 June; 5(2): 107-111 [An example of intra-genic cross-over (Also see G-Accra http://lib.bioinfo.pl/pmid:5722880)]
55. Konotey-Ahulu FID. Definition of Sickle Cell Trait and Sickle Cell Disease. Ghana Med J 1972; 11:417-420
56. Konotey-Ahulu FID. The Sickle-cell Diseases: Clinical manifestations including the sickle crisis. Arch Intern Med 1974; 133(4): 611-619 http://archinte.ama.assn.org/cgi/reprint/133/4/611-pdf
57. Noke Melissa, Peters Sarah, Ulph Fiona. A qualitative study to explore how professionals in the United Kingdom make decisions to test children for a sickle cell carrier state. Europ. Journal of Human Genetics 2016; 24:164-170. doi:10.1038/ejhg.2015.104 [Terms like “SC prevalence” and “not so benign nature of ‘SCT’” reveal ignorance of approved Terminology].
58. Konotey-Ahulu FID. Human Genetics Commission (HGC) and direct to consumer Genetic Tests, leading to Genetic Counseling. BMJ May 27 2009 http://www.bmj.com/cgi/eletters/338/may15_2/b1995#214256 Rapid Resp. [A HGC Report described Sickle Cell Trait as Sickle Cell Disorder]
59. Thompson Rachel. Europe Sickle Cell Disorders Market Highlights – 2015 http://www.researchandmarkets.com/publicationm/mnp5si6/europe_sicklecll_...
60. Serjeant GR, Serjeant B. Sickle Cell Disease, 3rd Ed, Oxford, OUP, 2001
61. Konotey-Ahulu Management of sickle cell disease patient in the community BMJ Rapid Response to Brousse V, Makali J, Rees DC: Management of sickle cell disease in the community. BMJ 2014;348:g1765 doi:10.1136/bmj.g1765 http://www.bmj.com/content/348/bmj.g1765/rr/694233 April 13 2014 [96 References]
62. NIH (Bethesda) “Sickle Cell Disease is the most common inherited blood disorder in the USA …” http://www.ghr.nlm.gov/condition/sickle-cell-disease
[But as Sickle Cell Trait is written SCT when SC is known to be disease phenotype what interpretation do people in the USA put on the recently widely advertised NIH home-use-kit for checking for the gene? Especially when the commercial Haemoglobin S Test-Tube Colour-Test does not differentiate between Sickle Cell Trait “AS” (1 Normal gene + 1 Abnormal gene) and Sickle Cell Disease “SC” phenotype (2 Abnormal genes)? See References 67 & 68.
63. BornGreat Evans. “I thought I was ‘AS’ but the tests show I am ‘SC’” On Facebook 13 December 2017.
64. Whiskey Delta Charlie “Here is what's possible if you are a carrier of Sickle Cell Trait” Facebook. September 22 at 4:21pm [Based on Lancet article Reference 40]
#sicklecellawarenessmonth #sicklecelltrait #exertion #Rhabdomyolysis http://dhmi.org/sickle-cell-trait-story/ April 2 & September 22 2016 · September is Sickle Cell Awareness Month. Awareness to Sickle Cell Trait the gene responsible for creating Warriors who live with Sickle Cell. Here is what's possible if you are a carrier of Sickle Cell Trait http://dhmi.org/sickle-cell-trait-story/ #sicklecellawarenessmonth #sicklecelltrait #exertion #Rhabdomyolysis http://www.sciencedirect.com/science/article/pii/S014067367105630?_rdoc=... Volume 298 Number 7736 page 1255. [See Reference 47 for criticism of Lancet article]
65. Streetly Allison. A national screening policy for sickle cell disease and thalassaemia major for the United Kingdom. BMJ 2000;320:1353 May 20. BMJ 2000; 320 doi: https://doi,org/10.1136/bmj.320.7246.1353
66. Konotey-Ahulu FID. Survey of sickle-cell disease in England and Wales. BMJ 1982; 284(6309): 112. doi:10.1136/bmj.284/6309/112-a (Jan. 9 1982) http://www.bmj.com/cgi/reprint/284/6309/112-a.pdf
67. Konotey-Ahulu FID. Detecting Sickle Haemoglobin. BMJ 1972; 2: 239 Nov 11; 4(5836) 376 See a Massachusetts law quoted below by Dr Beutler et al]
68. Beutler E, Boggs DR, Heller P, Maurer A, Motulsky AG, Sheehy TW. Hazards of indiscriminate screening for sickling. N Engl J Med. 1971 Dec 23;285(26):1485–1486 www.europepmc.org/articles/PMC178610 [Authors have commented on a Massachusetts Law which stated in part that “Every child, which the Commissioner of Public Health, by rule or regulation, may determine is susceptible to the disease known as sickle cell trait or sickle cell anemia, shall be required to have a blood test”. [How on earth does one explain to the Americans that there is no such thing as “the disease known as sickle cell trait?” Making my African NORMACHE = ACHEACHE?]
69. Konotey-Ahulu FID. Welcome to www.sicklecell.md The resource to the Sickle Cell Disease Patient. While there is a lot of information published on Sickle Cell Disease, there is comparatively less on the person with this hereditary affliction. This web site aims to correct the anomaly and be as complete a resource to the Sickle Cell Disease Patient as possible.
70. Konotey-Ahulu FID. Sickle Cell Disease in successive Ghanaian generations for Three Centuries from 1670 AD 1970. The Human Genome Diversity Project: Cogitations of An African Native. Politics and the Life Sciences (PLS) 1999, Vol 18: No 2, pp 317-322 https://www.cambridge.org/.../politics...lifesciences/.../90701926F3608D...... [Dr Konotey-Ahulu (“Dr Domeno”) and siblings in Generation VIII]
71. Haemoglobinopathy: The Genetics that touches you and me. [University of Cape Coast Golden Jubilee Message 2012 http://blog.sicklecell.md/sicklecell/sickle-cell-and-allied-haemoglobino...
72. Konotey-Ahulu FID. Genetic Counselling in sickle cell disease. BMJ 1969; 3: 235 http://www.bmj.com/cgi/reprint/3/5664/235.pdf (Put ‘ACHE’ for ‘BAD’) PERSONAL VIEW doi:10.1136/bmj.2.5648.48
73. Konotey-Ahulu FID. Sickle cell disease. The Case for Family Planning ASTAB Books Ltd, Accra, 1973
74. Konotey-Ahulu FID. Need for ethnic experts to tackle genetic public health. Lancet 2007; 370: 1836 [doi:10.1016/50140-6736(07)61771-1]
75. Konotey-Ahulu FID. Maintenance of high sickling rate in Africa: Role of polygamy. J Trop Med Hyg 1970 Jan; 73(1): 19-21 (38 References). [Traits who voluntarily restrict number of children they produce do diminish burden of abnormal haemoglobin disease (SS SC CC Sbeta-Thalassaemia Cbeta-Thalassaemia Thalassaemia Major SF CF Fbeta-Thalassaemia SKorle Bu SOsu-Christiansborg [ in the Ghanaian population. My MPSI shows that Males need more to heed this message for Voluntary Family Size Limitation].
76. Konotey-Ahulu FID, Kinderlerer, JL Lehmann H and Ringelhann B. Haemoglobin Osu-Christiansborg. A new chain variant of Haemoglobin A (beta 52 D3 Aspartic Acid to Asparagine) in combination with Haemoglobin ‘S’. J Med Genet 1971; 8(3): 302-305 http://pubmedcentral.nih.gov/picrender.fcgi?artid=146917&blobtype=pdf |
77. Bonney GE, Konotey-Ahulu FID. Polygamy and genetic equilibrium. Nature 1977; 265: 46-47 doi:10.1038/265046a0..n5589/pdf/265046a0.pdf
78. Konotey-Ahulu FID. Male procreative superiority index (MPSI): The missing co-efficient in African anthropogenetics. BMJ 1980; 291: 170
79. Konotey-Ahulu FID. The Male Procreative Superiority Index (MPSI): It’s relevance to genetical counselling. In FIFTY YEARS OF HUMAN GENETICS – A Festschrift and liber amicorium to celebrate the life and work of GEORGE ROBERT FRASER. Ed: Oliver Mayo & Carolyn Leach. Wakefield Press 2007, 1 The Parade West, Kent Town, Sth Australia www.wakefieldpress.com.au
80. NIH https://www.nhlbi.nih.gov/health-topics/sickle-cell-disease Couples who are planning to have children and know that they are at risk of having a child with sickle cell disease (SCD) may want to meet with a genetics counselor. A genetics counselor can answer questions about the risk and explain the choices that are available’
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Competing interests: I come from a Sickle Cell Disease Family: My Trait Parents produced 11 children: 3 disease-phenotype, 4 Traits, 4 with no abnormal Haemoglobin gene . I do not apologize for continuing to teach less knowledgeable people who do not come from a Sickle Cell Disease home.
I noted the article on genetic testing for non-specialists with great interest; increased genetic literacy amongst front-line healthcare professionals is of huge import due to the dramatic increase in range and scope of DNA genetic tests performed in the NHS is now underway but also because genetic testing is much ore widely in established than many realise due to lack of agreement of the term "genetic testing". The article gave a narrow definition of a genetic test; - “a process where this DNA is sequenced to look for changes in genetic makeup” with no reference as to source. I suggest that this is an incomplete definition and that the more appropriate definition of " a genetic testing" is that is given by the US National Institutes of Health which highlights that genetic tests are widely in use already and that genetic testing is not solely the terrain of those who run DNA testing services:-
“Genetic testing is a type of medical test that identifies changes in chromosomes, genes, or proteins. The results of a genetic test can confirm or rule out a suspected genetic condition or help determine a person’s chance of developing or passing on a genetic disorder…. Several methods can be used for genetic testing:
Molecular genetic tests (or gene tests) study single genes or short lengths of DNA to identify variations or mutations that lead to a genetic disorder.
Chromosomal genetic tests analyze whole chromosomes or long lengths of DNA to see if there are large genetic changes, such as an extra copy of a chromosome, that cause a genetic condition.
Biochemical genetic tests study the amount or activity level of proteins; abnormalities in either can indicate changes to the DNA that result in a genetic disorder.”
National Institutes of Health: Genetics Home reference: US National Library of Medicine @ https://ghr.nlm.nih.gov/primer/testing/genetictesting (accessed 18.10.17).
In my view genetic testing has been undertaken at scale, for example by screening laboratories, for some while. For example, in 2002 I led the establishment of a National Genetic screening programme which is now successfully embedded in the NHS in England and detects and counsels thousands of genetic carriers each year – the NHS Sickle Cell and Thalassaemia Screening programme. (https://phescreening.blog.gov.uk/category/sct/) .
The NIH definition implies that genetic tests are widely in use already and that genetic testing is not solely the terrain of those who run DNA testing services. It highlights why increased genetic literacy for ALL healthcare professionals is important now, and the importance of developing a realistic and affordable approach to counselling of individuals about genetic findings informed by understanding of genotype phenotype interactions.
It also emphasises that genetic education of the whole population is ethically important to ensure that individuals have a good understanding of what the implications of findings are, before they have to face difficult choices rather than in the middle of such a situation, in particular as common gene tests for relatively common conditions such as Sickle Cell and Familial Hypercholesterolemia re performed not just DNA tests for rare variants. A quick scan of the internet will show that a range of definitions of genetic testing are used.
A common definition which we all agree is an important and early step in getting communication clear both for professionals and also importantly the public as genetics is recognising as "for us all" and not only "for experts".
Competing interests: I set up and ran the NHS Sickle Cell and Thalassaemia Screening programme between 2001-2013. This is genetic screening programme which highlighted many aspects and challenges relating to genetic testing.