#RareDiseaseDay recently passed, but at Annals of Human Genetics, weβre proud of the research published. The work of our authors helps to shorten the diagnostic odyssey and advance new treatments.
Explore a recent review that reflects on how genomics has transformed rare disease diagnosis and care.
#HGM2026 in Athens will focus on latest developments in human genomics.
#TheGoldenHelixFoundation
This April join #HGM2026 in Athens to hear about breakthroughs in human genomics!
#TheGoldenHelixFoundation
#HGM2026 welcomes Prof. Isidore Rigoutsos (Thomas Jefferson University) as an invited speaker. He will present on computational genomics, regulatory networks, and systems-level genome analysis.
Visit www.hugo-hgm2026.org!
#TheGoldenHelixFoundation
#HGM2026 welcomes Prof. Aime Lumaka (University of Kinshasa) as an invited speaker. He will discuss genomics research in African populations and its implications for global health and medicine.
Visit www.hugo-hgm2026.org!
#TheGoldenHelixFoundation
Figure 7 Genetic and molecular adaptations to hypoxia in native high-altitude populations.
An Early View: #Genetic analysis of Sherpa highlanders shows adaptive variants in EPAS1 and EGLN1 linked to reduced gene expression and a blunted EPO response under chronic hypoxia. This offers insight into human high-altitude adaptation.
π Read the full article: doi.org/10.1111/ahg....
Attend #HGM2026 in April in Athens to hear from leading voices in human genomics!
#TheGoldenHelixFoundation
Less than 80 days to the Human Genome Meeting!
#HGM2026 #TheGoldenHelixFoundation
An Early View: Mitonuclear discordance has been proposed to impair #mitochondrial function in admixed populations.
In 2,301 MΔori and Pacific peoples in Aotearoa New Zealand, higher discordance was associated with lower risk of #gout and #T2DM, particularly in the prevalent B4a1a mtDNA haplogroup.
Patients with different CARS levels have different responses to therapies. A total of 373 HCC samples were divided into high- and low-CARS groups based on the median value, and the IC50 values for different drugs were estimated for each HCC patient according to a pipeline from the Genomics of Drug Sensitivity in Cancer (GDSC) database (AβC). (A) For sorafenib, CARShigh patients have significantly higher IC50 values than CARSlow patients. (B) For tamoxifen, CARShigh patients have significantly lower IC50 values than CARSlow patients. (C) For docetaxel, CARShigh patients have significantly lower IC50 values than CARSlow patients. (DβF) The βTIDEβ algorithm was applied to assess the T cell exclusion and T cell dysfunction levels in HCCs. (D) Higher CARS is associated with lower TIDE scores. Lower TIDE scores indicate greater sensitivity to ICI therapy. (E) CARShigh patients experience significantly less loss of T-cell function compared to CARSlow patients. (F) CARShigh patients exhibit higher levels of T-cell exclusion grade in tissue than CARSlow patients.
An Early View: Single-cell transcriptomics in #hepatocellular #carcinoma identifies a rare cancer stem-like cell population and Cancer Stem-like Cell Risk Score (CARS).
Higher CARS predicted poorer survival, increased drug resistance and drug sensitivity.
π: onlinelibrary.wiley.com/doi/10.1111/...
(a) Pedigree of Family-1 segregating c.1579C > T; p.Pro527Ser novel ADGRG1 variant. (b) Pedigree of Family-2 segregating c.649A > C; p.Met217Leu variant. (c) Pedigree of Family-3 segregating c.722T > G; p.Leu241Ter variant. (d) Genomic location at chr16 and a part of the sequence chromatogram showing the c.1579C > T variant in ADGRG1 gene associated with bilateral frontoparietal polymicrogyria (BFPP); the mother was a heterozygous carrier, whereas the unaffected sibling was homozygous normal and the affected individuals were homozygous mutant for this ADGRG1 variant. (e) Genomic location at chr16 and a part of the sequence chromatogram showing the c.649A > C variant in KAT8 gene associated with LIGOWS syndrome (syndromic intellectual disability); unaffected individuals of the family were heterozygous carriers, and the affected individuals were homozygous mutants for this KAT8 variant. (f) Genomic location at chr7 and a part of sequence chromatogram showing the c.722T > G variant in FAM126A gene associated with hypomyelination and congenital cataract; unaffected individuals of the family were heterozygous carriers, and the affected individual was homozygous mutant for this FAM126A variant.
An Early View: #Exome sequencing of three rare neurological disorders in three unrelated Pakistani families revealed novel pathogenic variants in ADGRG1, KAT8, and FAM126A, expanding the allelic and geographic spectrum of neurological disorders.
π: onlinelibrary.wiley.com/doi/10.1111/...
Figure 1: A flowchart describing the steps of WGS analysis in the study
Today is World Pancreatic Cancer Dayπͺ
Pancreatic cancer is the 6th deadliest globally, with a five-year survival rate under 10%.
We highlight work in The Annals using whole-genome sequencing to identify rare variants in familial pancreatic cancer:
onlinelibrary.wiley.com/doi/10.1111/...
Figure 2: Morphology and ultrastructure analysis of spermatozoa in the fertile male and the man harbouring CFAP74 variants. (A) Morphology analysis of the spermatozoa from a fertile man and the proband P24 by modified Papanicolaou staining. (B) SEM analysis of spermatozoa cells from a control individual and the proband P24. The thinner midpiece was marked with a yellow arrow. (C) TEM analysis of spermatozoa ultrastructure. A cross section of sperm from a control participant displayed the typical β9 + 2β microtubule structure with CP, nine pairs of peripheral DMT and an arrangement of ODF. Longitudinal section of the control participant displayed organized MS in flagella. Compared with the control, abnormal sperm ultrastructure could be observed in the proband P24. CP, central pair; DMT, doublet microtubule; MS, mitochondrial sheaths; MT, mitochondria; ODF, outer dense fibre; SEM, scanning electron microscopy; TEM, transmission electron microscopy.
An Early View: Whole-exome sequencing of 44 men with #asthenoteratozoospermia identified CFAP74 variants as potential causes of male #infertility.
Novel compound heterozygous and homozygous CFAP74 mutations were linked to flagellar defects and disrupted sperm morphology.
π: doi.org/10.1111/ahg....
Figure 1: Distribution of LDL cholesterol levels by gene with identified variants (patients P1βP23).
An Early View: A study of 133 children with suspected dyslipidemia in TΓΌrkiye used targeted NGS to explore the genetic basis of #pediatric lipid disorders.
Pathogenic variants were seen in 17% of cases, most often in LDLR, with novel variants found in LDLRAP1 and APOB.
π: doi.org/10.1111/ahg....
Figure 1: Identification of the candidate c.118-4dup TMEM256 and c.1123G > A MYH3 variants. (A) The pedigree of the family, an arrowhead indicates the proband. Affected family members and non-penetrant carriers carrying the monoallelic TMEM256+/V and/or MYH3+/V variants are labeled in bold, while the wild-type genotypes (TMEM256+/+ and MYH3+/+) are indicated as WT.
An Early View: Findings from five-generation Polish family identified TMEM256 as a novel candidate gene for #clubfoot and implicates a known MYH3 variant in arthrogrypotic hand deformities.
π: onlinelibrary.wiley.com/doi/10.1111/...
Figure 1: A schematic overview summarizing the study. GWAS stands for genome-wide association study; SNPs refer to single-nucleotide polymorphism; MR denotes Mendelian randomization; IVW signifies inverse-variance-weighted; and MR-PRESSO represents MR pleiotropy residual sum and outlier.
An Early View: A Mendelian randomization + bioinformatics study revealed 20 lipids that have a potential causal relationship with #Alzheimer's disease, #Parkinson's disease & epilepsy.
Findings suggest lipids may serve as biomarkers & therapeutic targets.
π: onlinelibrary.wiley.com/doi/full/10....
Today marks World Alzheimerβs Day π
In support of eliminating #Alzheimerβs disease, we highlight research published in The Annals that advances this objective.
π FSH and AD: onlinelibrary.wiley.com/doi/10.1111/...
π Drosophila amyloid toxicity model for AD: onlinelibrary.wiley.com/doi/10.1111/...
Figure 1: The Sanger sequencing results of the proband and parents for the variants.
An Early View: A study reports a novel STAG1 splice-site variant linked to intellectual disability.
Whole exome sequencing and functional assays confirmed aberrant splicing, broadening the mutational and phenotypic spectrum of STAG1-related disorders.
π: onlinelibrary.wiley.com/doi/10.1111/...
Figure 1: Geographical location of the study area and distribution of urban communities in Buenaventura, Valle del Cauca, Colombia. The figure shows the position of Buenaventura on the Pacific coast of Colombia, with its 12 urban communities highlighted. Communities 1 to 5 are located in the insular zone, while communities 6 to 12 are part of the continental zone. From Ortega et al. (2015). Licensed under CC BY 4.0: https://creativecommons.org/licenses/by/4.0/. Modified from original. Available at https://academicjournals. org/journal/IJGMB/article-abstract/8E4460450921.
An Early View: A study of 819 individuals from Buenaventura, Colombia, examined 5 key variants linked to #malaria resistance.
Resistance genotypes were most frequent in young adults (13β26) and insular communities, suggesting local adaptation.
π: onlinelibrary.wiley.com/doi/full/10....
Thanks for highlighting our Centenary Issue! Weβre thrilled to mark this milestone ππ
Cover image of The Annals of Human Genetics centenary issue.
The Centenary Special Issue of The Annals of Human Genetics is now available!
First published in 1925, this special issue celebrates recent advances in human genetics, and features contributions from 13 @ucl.ac.uk researchers.
Check out the issue online: onlinelibrary.wiley.com/toc/14691809...
Cover image of the Annals of Human Genetics Centenary Special Issue
π’The Annals of Human Genetics marks 100 years!π
Our Centenary Special Issue reflects on the journalβs history while celebrating recent advances and current investigations in human genetics, from statistical #genetics to #genomic medicine.
π Read here: onlinelibrary.wiley.com/toc/14691809...
Figure 3 Scheme of gene interactions according to the String database: (A) genes associated with no response; (B) genes associated with good response (disconnected nodes were hidden from the network).
An Early View: Whole #exome sequencing in locally advanced rectal #cancer (LARC) reveals variants in SLC16A6 & SLC25A2 linked with poor neoadjuvant chemoradiotherapy (nCRT) response.
Findings point towards variants as predictors for tailored nCRT in LARC.
onlinelibrary.wiley.com/doi/10.1111/...
An Early View: A systematic review of 33 GWAS-based polygenic risk score studies for #cancer in African ancestry populations highlights limited validation & clinical utility.
The authors call for more ancestry-specific #GWAS and standardized reporting to improve precision cancer risk prediction.
An Early View: A new commentary by @andyjmwalton.bsky.social, Dr Aylward, Prof Thomas, and βͺDr @adamrutherford.bsky.social revisit the intellectual origins of #panmixia, revealing how essentialist assumptions shaped its early adoption in evolutionary theory, long before the Modern Synthesis.
Figure 1: The pedigree illustrates segregation analysis of LOXHD1 variants: c.2879C>A, p.(Ser960Ter), and c.1441C>T, p.(Pro481Ser). The father is heterozygous for variant c.2879C>A, p.(Ser960Ter), and the mother is heterozygous for variation c.1441C>T, p.(Pro481Ser). The affected siblings with hearing loss inherited one variant from each parent, resulting in compound heterozygosity, consistent with an autosomal recessive inheritance pattern.
An Early View: A new case report identifies compound heterozygousβ―LOXHD1β―variants in a North Indian family with ARNSHL, expanding the geneβs allelic and regional diversity.
Supports a broader inclusion ofβ―LOXHD1β―in diagnostic panels.
πRead the full letter: onlinelibrary.wiley.com/doi/full/10....
An Early View: #Genetic evidence supports a causal link between #GERD and myocardial infarction (MI).
Using Mendelian randomization, researchers found MI risk is partly mediated by hypertension and type 2 diabetes.
πRead the full article: onlinelibrary.wiley.com/doi/full/10....
World #Hepatitis Day π
Despite vaccines and cures, hepatitis remains the 2nd leading infectious cause of death globally (@who.int).
We highlight Annals research on how host genetics shape chronic Hepatitis C.
π: onlinelibrary.wiley.com/doi/10.1111/...
π: onlinelibrary.wiley.com/doi/10.1111/...
An Early View: A population #genetics study evaluated a custom 41-marker multi-InDel system for its forensic efficacy and ability to capture genetic diversity in Chinese Hezhou and Southern Shaanxi Han populations.
πRead the full article: onlinelibrary.wiley.com/doi/full/10....
An Early View: A new review by Prof Van Steensel (@4dmanifold.bsky.social) reframes acne as a disease of sebaceous progenitor cells, with #GWAS and molecular data implicating stem cell dynamics and Wingless signaling. This challenges long-held assumptions and points toward new therapeutic targets.
