Evidence map›Paper›PMID 42693638›Full record

ArticleHGG advances2026

Mapping long-read sequences to a complete reference genome reveals uncaptured variants across the β-Globin cluster in Africans with sickle cell disease.

Pamela Lurie, Medhat Mahmoud, Aparna Haldipur, Yixing Han, Qing Li, Edmond Wonkam Tingang, Natalie Asmus, Emilyn Banfield, Nancy J Hall, Bamidele Tayo and 15 more

Abstract read
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In one paragraph

Article in HGG advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

25 authors.

Pamela LurieDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA; USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX, USA; Childhood Complex Disease Genomics Section, Center for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Medhat MahmoudHuman Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
Aparna HaldipurChildhood Complex Disease Genomics Section, Center for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Yixing HanChildhood Complex Disease Genomics Section, Center for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Qing LiChildhood Complex Disease Genomics Section, Center for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Edmond Wonkam TingangChildhood Complex Disease Genomics Section, Center for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Natalie AsmusChildhood Complex Disease Genomics Section, Center for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Emilyn BanfieldChildhood Complex Disease Genomics Section, Center for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Nancy J HallDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA; USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX, USA.
Bamidele TayoDepartment of Public Health Sciences, Parkinson School of Health Sciences and Public Health, Loyola University Chicago, Maywood, IL, USA.
Richard CooperDepartment of Public Health Sciences, Parkinson School of Health Sciences and Public Health, Loyola University Chicago, Maywood, IL, USA.
Titilola AkingbolaDepartment of Hematology, University of Ibadan, College of Medicine, University College Hospital, Ibadan, Nigeria.
George AyodoSchool of Health Sciences, Jaramogi Oginga Odinga University of Science and Technology, Bondo, Kenya.
Stephen ObaroInternational Foundation Against Infectious Disease in Nigeria, Gwarimpa Abuja, Nigeria; Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA.
Guillaume LettreMontreal Heart Institute and Department of Medicine, Faculty of Medicine, Université de Montreal, Montreal, QC, Canada.
Qing MengHuman Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
Shalini JhangianiHuman Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
R Alan HarrisDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
Kim C WorleyDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
Juyhun KimCenter for Genomics and Data Science Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
Arang RhieCenter for Genomics and Data Science Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Adam M PhillippyCenter for Genomics and Data Science Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Fritz SedlazeckDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA; Department of Computer Science, Rice University, 6100 Main Street, Houston, TX, USA.
Ambroise WonkamMcKusick-Nathans Institute & Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Division of Human Genetics, University of Cape Town, Cape Town, South Africa.
Neil A HanchardDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA; USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX, USA; Childhood Complex Disease Genomics Section, Center for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address: neil.hanchard@nih.gov.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

African genomes are marked by extensive complexity in the number and distribution of variants yet remain under-represented in genetic databases and the human reference genome. This gap in representation limits the broad application of genomic medicine. Sickle cell disease (SCD)-one of the most common monogenic diseases-has its highest prevalence in Africa, and variation in disease severity has consistently been linked to the β-globin locus, including levels of fetal hemoglobin (HbF). Modulation of HbF is central to current SCD gene therapies; however, the inherent complexity and variation at the locus in African genomes present a challenge to translating these advances to Africa. Here, we align single-molecule long-read sequencing (LRS) targeted to the β-globin region to the human genome build 38 (hg38) and telomere-to-telomere (T2T)-CHM13.v2 genome references in 40 individuals with SCD, predominantly recruited from three African countries. We demonstrate that the expanded T2T-CHM13.v2 reference sequence at this locus reduces structural variant (SV) calls by 70% and uncovers uncaptured single-nucleotide variants (SNVs). Across the cluster, we report 343 SVs and 196 SNVs that have not been previously reported, including in LRS data from the All of Us project. By including African populations from ethnolinguistic groups that have not been previously surveyed, we improve variant resolution and bolster evidence for observed variation. Finally, we identify a common ∼4 kb insertion locus overlapping the HBB promoter among individuals with high HbF. These results demonstrate the utility of combining a comprehensive reference genome with LRS in African populations to uncover genomic variation at disease-associated loci.

Indexed as

Anemia, Sickle Cellbeta-GlobinsGenome, HumanBlack PeopleFetal HemoglobinGenetic VariationHumansMultigene FamilyPolymorphism, Single NucleotideSub-Saharan African Peoplebeta-GlobinsFetal HemoglobinAfrican genomicscis-regulatory variationfetal hemoglobingenomic diversityHBBhuman genomesickle haplotypesstructural variationT2T-CHM13

Identifiers

PMID42693638

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.