Finnish heritage disease
A Finnish heritage disease is a genetic disease or disorder that is significantly more common in people whose ancestors were ethnic Finns, natives of Finland and Sweden (Meänmaa) and Russia (Karelia and Ingria). There are 36 rare diseases regarded as Finnish heritage diseases.[1] The diseases are not restricted to Finns; they are genetic diseases with far wider distribution in the world, but due to founder effects and genetic isolation they are more common in Finns.
Within Finland these diseases are more common in the east and north, consistent with their higher association with ethnic Finns than with ethnic Swedes.[2] The Finnish disease heritage does not extend to other ethnic groups in the region, the Sámi and Karelians other than Finnish Karelians. It is attributed to a population bottleneck among ancestors of modern Finns, estimated to have occurred about 4000 years ago, presumably when populations practicing agriculture and animal husbandry arrived in Finland.[3]
In Finland about one in five persons carries a gene defect associated with at least one Finnish heritage disease, and about one in 500 children born is affected.[4] Most of the gene defects are autosomal recessives, so that if both the mother and father carry the same defect, the chance that their child will have the associated disease is 1 in 4. The molecular genetics of many of these diseases have been determined, enabling genetic testing, prenatal testing, and counseling. This has raised questions of bioethics and eugenics.[5]
Finnish heritage disease types
There are 36 identified Finnish heritage diseases:[6][7]
- Amyloidosis, Finnish type
- Lethal arthrogryposis with anterior horn cell disease
- Aspartylglucosaminuria
- Autoimmune polyendocrinopathy syndrome, type I, with or without reversible metaphyseal dysplasia
- Cartilage–hair hypoplasia
- Ceroid lipofuscinosis, neuronal, 1
- Ceroid lipofuscinosis, neuronal, 3
- Ceroid lipofuscinosis, neuronal, 5
- Ceroid lipofuscinosis, neuronal, 8, Northern epilepsy variant (Synonyms: Northern epilepsy; Epilepsy, progressive, with mental retardation)
- Choroideremia
- Cohen syndrome
- Cornea plana 2
- Diarrhea 1, secretory chloride, congenital
- Diastrophic dysplasia
- Epilepsy, progressive myoclonic 1A (Unverricht–Lundborg)
- Glycine encephalopathy (Nonketotic hyperglycinemia)
- GRACILE syndrome
- Gyrate atrophy of choroid and retina
- Hydrolethalus syndrome 1
- Infantile-onset spinocerebellar ataxia (Mitochondrial DNA depletion syndrome 7)
- Lactase deficiency, congenital
- Lethal congenital contracture syndrome 1
- Lysinuric protein intolerance
- Meckel syndrome
- Megaloblastic anemia-1, Finnish and Norwegian type
- Mulibrey nanism
- Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 3
- Nephrotic syndrome, type 1 (Finnish congenital nephrosis)
- Ovarian dysgenesis 1
- Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (Nasu–Hakola disease)
- Progressive encephalopathy with Edema, Hypsarrhythmia and Optic atrophy
- RAPADILINO syndrome
- Retinoschisis 1, X-linked, juvenile
- Sialuria, Finnish type (Salla disease)
- Tibial muscular dystrophy, tardive
- Usher syndrome, type 3A
Out of these, three are rare causes of dwarfism: cartilage–hair hypoplasia, diastrophic dysplasia and Mulibrey nanism.
Four genetically distinct subtypes of neuronal ceroid lipofuscinosis are found in the Finnish heritage: CLN1, CLN3, CLN5, and CLN8.[8] Names for conditions associated with these subtypes include infantile neuronal ceroid lipofuscinosis, Jansky–Bielschowsky disease and northern epilepsy syndrome. As of 2001, CLN5 and CLN8 had been reported almost exclusively in Finland.[8]
Meckel syndrome type 1 (MKS1[9]), a lethal condition, is known in 48 Finnish families.[10]
Other genetic diseases
The European Organization for Rare Diseases (EURORDIS) estimates that there are between 5,000 and 7,000 distinct rare diseases, affecting between 6% and 8% of the population of the European Union.[11] The majority of genetic diseases reported in Finland are not part of the Finnish disease heritage and their prevalence is not higher in Finland than worldwide.
Some genetic diseases are disproportionately rare in Finns. These include cystic fibrosis and phenylketonuria. In Finland, about 1 in 80 persons are carriers of a cystic fibrosis mutation, compared with an average of 1 in 25 elsewhere in Europe.[12]
Genetic history
Based on molecular data, a population bottleneck among ancestors of modern Finns is estimated to have occurred about 4000 years ago.[3] This bottleneck resulted in exceptionally low diversity in the Y chromosome, estimated to reflect the survival of just two ancestral male lineages.[13][14] The distribution of Y chromosome haplotypes within Finland is consistent with two separate founding settlements, in eastern and western Finland.[15] The Finnish disease heritage has been attributed to this 4000-year-old bottleneck.[3] The geographic distribution and family pedigrees associated with some Finnish heritage disease mutations has linked the enrichment in these mutations to multiple local founder effects, some associated with a period of "late settlement" in the 16th century (see History of Finland).[16]
Etymology
Although the concept is older, the English term "Finnish disease heritage" first appears in the medical literature in the 1990s. One of the earliest uses is in the translated title of a 1994 medical article,[17] soon followed by others.[3][18]
See also
References
- Norio R (May 2003). "The Finnish Disease Heritage III: the individual diseases". Human Genetics. 112 (5–6): 470–526. doi:10.1007/s00439-002-0877-1. PMID 12627297. S2CID 26741302.
- Palo JU, Ulmanen I, Lukka M, Ellonen P, Sajantila A (April 2009). "Genetic markers and population history: Finland revisited". European Journal of Human Genetics. 17 (10): 1336–46. doi:10.1038/ejhg.2009.53. PMC 2986642. PMID 19367325.
- Sajantila A, Salem AH, Savolainen P, Bauer K, Gierig C, Pääbo S (October 1996). "Paternal and maternal DNA lineages reveal a bottleneck in the founding of the Finnish population". Proceedings of the National Academy of Sciences of the United States of America. 93 (21): 12035–9. Bibcode:1996PNAS...9312035S. doi:10.1073/pnas.93.21.12035. PMC 38178. PMID 8876258.
- Kallinen J, Heinonen S, Palotie A, Mannermaa A, Ryynanen M (May 2001). "Antenatal gene tests in low-risk pregnancies: molecular screening for aspartylglucosaminuria (AGU) and infantile neuronal ceroid lipofuscinosis (INCL) in Finland". Prenatal Diagnosis. 21 (5): 409–12. doi:10.1002/pd.82. PMID 11360285.
- Seppo Poutanen (2005). "3: The first genetic screening in Finland: its execution, evaluation, and some possible implications for liberal government". In Robin Bunton; Alan Petersen (eds.). Genetic governance: Health, risk, and ethics in the biotech era. Routledge. p. 215. ISBN 0-415-35407-2.
- "The Finnish Disease Heritage". FinDis. Retrieved 4 March 2018.
- "Diseases". FinDis. Retrieved 4 March 2018.
- Krystyna E. Wiśniewski; Nanbert Zhong; Jeffrey C. Hall (2001). Batten disease: diagnosis, treatment, and research. Academic Press. p. 243. ISBN 0-12-017645-9. page 125
- Consugar MB, Kubly VJ, Lager DJ, Hommerding CJ, Wong WC, Bakker E, Gattone VH, Torres VE, Breuning MH, Harris PC (June 2007). "Molecular diagnostics of Meckel–Gruber syndrome highlights phenotypic differences between MKS1 and MKS3". Human Genetics. 121 (5): 591–9. doi:10.1007/s00439-007-0341-3. PMID 17377820. S2CID 11815792.
- Salonen R.; Opitz, John M.; Reynolds, James F. (August 1984). "The Meckel syndrome: clinicopathological findings in 67 patients". American Journal of Medical Genetics. 18 (4): 671–89. doi:10.1002/ajmg.1320180414. PMID 6486167.
- "Rare Diseases: Understanding This Public Health Priority" (PDF). European Organisation for Rare Diseases (EURORDIS). November 2005. Retrieved 16 May 2009.
- Hytönen M, Patjas M, Vento SI, Kauppi P, Malmberg H, Ylikoski J, Kere J (December 2001). "Cystic fibrosis gene mutations deltaF508 and 394delTT in patients with chronic sinusitis in Finland". Acta Oto-Laryngologica. 121 (8): 945–7. doi:10.1080/000164801317166835. PMID 11813900.
- Kittles RA, Bergen AW, Urbanek M, Virkkunen M, Linnoila M, Goldman D, Long JC (April 1999). "Autosomal, mitochondrial, and Y chromosome DNA variation in Finland: evidence for a male-specific bottleneck" (PDF). American Journal of Physical Anthropology. 108 (4): 381–99. doi:10.1002/(SICI)1096-8644(199904)108:4<381::AID-AJPA1>3.0.CO;2-5. PMID 10229384.
- Lahermo P, Savontaus ML, Sistonen P, Béres J, de Knijff P, Aula P, Sajantila A (1999). "Y chromosomal polymorphisms reveal founding lineages in the Finns and the Saami". European Journal of Human Genetics. 7 (4): 447–58. doi:10.1038/sj.ejhg.5200316. PMID 10352935.
- Kittles RA, Perola M, Peltonen L, Bergen AW, Aragon RA, Virkkunen M, Linnoila M, Goldman D, Long JC (May 1998). "Dual origins of Finns revealed by Y chromosome haplotype variation". American Journal of Human Genetics. 62 (5): 1171–9. doi:10.1086/301831. PMC 1377088. PMID 9545401.
- Peltonen L, Jalanko A, Varilo T (1999). "Molecular genetics of the Finnish disease heritage". Human Molecular Genetics. 8 (10): 1913–23. doi:10.1093/hmg/8.10.1913. PMID 10469845.
- de la Chapelle A, Hästbacka J, Lehesjoki AE, Sulisalo T, Kere J, Tahvanainen E, Sistonen P (1994). "[Linkage and linkage disequilibrium in the Finnish disease heritage]". Duodecim; Lääketieteellinen Aikakauskirja (in Finnish). 110 (7): 654–64. PMID 8542820.
- Perheentupa J (October 1995). "The Finnish disease heritage: a personal look". Acta Paediatrica. 84 (10): 1094–9. doi:10.1111/j.1651-2227.1995.tb13501.x. PMID 8563216. S2CID 29999767.