Demographic Events and Evolutionary Forces Shaping European Genetic Diversity

Veeramah, Krishna R.; Novembre, John

doi:10.1101/cshperspect.a008516

Cited by 17 publications

(20 citation statements)

References 56 publications

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“…More recently, the Iberian diaspora initiated in the XV century with the maritime expansion could have contributed to the spread of the S allele in sub-Saharan Africa and in Central and South America. 50,64,66 The M Malton , M Palermo , M Nichinan , Q0 LaPalma and S Iiyama Alleles…”

Section: The S Allele and The Pglu264val Mutationmentioning

confidence: 99%

“…To date, it is well accepted that the genetic variability within Europe mirrors the local geography, and the observed gradients are likely to result from several population movements towards the north, like the ones associated with the expansion of agriculturalists during Neolithic times. 50 Furthermore, the larger sustained population sizes in Southern European regions, because of their improved long-term survival conditions, are likely to have contributed as well to their larger genetic diversity. 50 In summary, the updated knowledge of human genetic variation discards, not only a Scandinavian origin of the Z allele but also any linked benefit to its carries.…”

Section: Common and Rare Aat Variantsmentioning

confidence: 99%

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Known Mutations at the Cause of Alpha-1 Antitrypsin Deficiency an Updated Overview of SERPINA1 Variation Spectrum

Seixas

Marques

2021

TACG

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Alpha-1-Antitrypsin deficiency (AATD), caused by SERPINA1 mutations, is one of the most prevalent Mendelian disorders among individuals of European descend. However, this condition, which is characterized by reduced serum levels of alpha-1-antitrypsin (AAT) and associated with increased risks of pulmonary emphysema and liver disease in both children and adults, remains frequently underdiagnosed. AATD clinical manifestations are often correlated with two pathogenic variants, the Z allele (p. Glu342Lys) and the S allele (p.Glu264Val), which can be combined in severe ZZ or moderate SZ risk genotypes. Yet, screenings of AATD cases and large sequencing efforts carried out in both control and disease populations are disclosing outstanding numbers of rare SERPINA1 variants (>500), including many pathogenic and other likely deleterious mutations. Generally speaking, pathogenic variants can be subdivided into either loss-or gain-of-function according to their pathophysiological effects. In AATD, the loss-of-function is correlated with an uncontrolled activity of elastase by its natural inhibitor, the AAT. This phenomenon can result from the absence of circulating AAT (null alleles), poor AAT secretion from hepatocytes (deficiency alleles) or even from a modified inhibitory activity (dysfunctional alleles). On the other hand, the gain-of-function is connected with the formation of AAT polymers and their switching on of cellular stress and inflammatory responses (deficiency alleles). Less frequently, the gain-of-function is related to a modified protease affinity (dysfunctional alleles). Here, we revisit SERPINA1 mutation spectrum, its origins and population history with a greater emphasis on variants fitting the aforementioned processes of AATD pathogenesis. Those were selected based on their clinical significance and wider geographic distribution. Moreover, we also provide some directions for future studies of AATD clinically heterogeneity and comprehensive diagnosis.

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Section: The S Allele and The Pglu264val Mutationmentioning

confidence: 99%

Section: Common and Rare Aat Variantsmentioning

confidence: 99%

Known Mutations at the Cause of Alpha-1 Antitrypsin Deficiency an Updated Overview of SERPINA1 Variation Spectrum

Seixas

Marques

2021

TACG

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“…In this collection, scholars of genetic variation and evolution in the major geographic regions of the world have outlined both known and more recent genetic studies (Gomez et al 2014;Majumder and Basu 2014;Ruiz Linares 2014;Veeramah and Novembre 2014). Their research, and the complementary works of others, allows us to make three major novel inferences.…”

Section: A Brief Synthesis Of Recent Human Evolutionmentioning

confidence: 99%

Perspectives on Human Variation through the Lens of Diversity and Race: Figure 1.

Chakravarti

2015

Cold Spring Harb Perspect Biol

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“…Studies of European genetic diversity continue to untangle how people settled and migrated through Europe and adapted to their environment. 1 Although most of the present-day European populations are wellstudied, some isolated populations, like the Roma (Romani, Gypsy), are not that well known yet. The Roma, a large transnational minority population numbering more than 15 million people worldwide, 10-12 million of whom live in Europe, originate from India.…”

Section: Introductionmentioning

confidence: 99%

The variability of multi-drug resistance ABCB1 gene in the Roma population from Croatia

Petranović

Tomas

Škarić‐Jurić

et al. 2019

Mol. exp. biol. med.

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When overexpressed, a large transmembrane P-glycoprotein, the product of the ABCB1 gene, is a notable impediment to brain-targeted therapies (like antiepileptics) and chemotherapies. Some of the genetic biomarkers with evidence of multi-drug resistance in ABCB1 ― rs1045642, rs1128503, and rs3213619 ― were analyzed in 440 subjects, members of three socio-culturally different Roma (Gypsy) groups of Croatia. Minor allele frequencies (MAFs) of rs1045642 and rs1128503 were the highest in the Balkan Roma (63.6% and 69.4%, respectively) when compared to the Baranja (52.3% and 62.5%) and the Međimurje Roma (48.8% and 54.5%) (p=0.0005 and p=0.0011, respectively). rs3213619 was monomorphic in the Međimurje group, while its MAFs in other two Roma groups were very low (<1.9%). The distribution of five detected haplotypes (four in the Međimurje group) significantly differed between the Roma subpopulations (p<0.0001), just like the frequencies of diplotypes (p=0.0008). At a global scale, the positive relationship between genetic and geographic distances between the 21 investigated populations indicates isolation by spatial distance. However, this is not true for the relationship between Roma and other populations due to their population history. The analyzed ABCB1 loci indicate genetic distinctiveness of the Roma population.

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Demographic Events and Evolutionary Forces Shaping European Genetic Diversity

Cited by 17 publications

References 56 publications

Known Mutations at the Cause of Alpha-1 Antitrypsin Deficiency an Updated Overview of SERPINA1 Variation Spectrum

Known Mutations at the Cause of Alpha-1 Antitrypsin Deficiency an Updated Overview of SERPINA1 Variation Spectrum

Perspectives on Human Variation through the Lens of Diversity and Race: Figure 1.

The variability of multi-drug resistance ABCB1 gene in the Roma population from Croatia

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