When close relatives are forced to reproduce, the resulting offspring inherit above average homozygosity and reduced fitness. Biologists now recognize inbreeding depression in the wild, a phenomenon that will probably increase as natural populations become depleted and fragmented. Inbreeding depression is most commonly expressed as compromised fertility and embryogenesis, but actual mechanisms remain poorly understood, especially for wild populations. Here, we examine how reduced heterozygosity influences spermatozoal and gonadal traits in wild rabbits (Oryctolagus cuniculus) sampled across the United Kingdom. By using a suite of 29 microsatellite markers (analyzed to confirm representation of individual heterozygosity across our sample), we found a significant negative relationship between heterozygosity and the production of normal sperm; the relationship was significant both between (n = 12) and within (n = 91 [total males], 42 [island], 49 [mainland]) populations. Reduced heterozygosity was also associated with decreased testis size across males (n = 112), but no relationship was seen at the population level, suggesting environmental confounds. Our results show, for a wild mammal, that inbreeding is associated with decreased sperm quality, confirming suggestions of links between inbreeding and elevated sperm abnormalities in rare felids . These findings could explain why inbreeding depression so frequently arises via compromised fertility and embryogenesis .
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http://dx.doi.org/10.1016/j.cub.2006.02.059 | DOI Listing |
Med
January 2025
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R. China. Electronic address:
Background: The genomic landscape of esophageal squamous cell carcinoma (ESCC) has been characterized extensively, but there remains a significant need for actionable targets and effective therapies.
Methods: Here, we perform integrative analysis of genome-wide loss of heterozygosity and expression to identify potential tumor suppressor genes. The functions and mechanisms of one of the candidates, TACC2, are then explored both in vitro and in vivo, leading to the proposal of a therapeutic strategy based on the concept of synthetic lethality.
Elife
January 2025
Department of Neurology, Baylor College of Medicine, Houston, United States.
Front Endocrinol (Lausanne)
January 2025
Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
Introduction: The sodium/iodide symporter (NIS) mediates active iodide accumulation in the thyroid follicular cell. Biallelic loss-of-function variants in the NIS-coding gene cause congenital dyshormonogenic hypothyroidism due to a defect in the accumulation of iodide, which is required for thyroid hormonogenesis.
Objective: We aimed to identify, and if so to functionally characterize, novel pathogenic gene variants in a patient diagnosed with severe congenital dyshormonogenic hypothyroidism characterized by undetectable radioiodide accumulation in a eutopic thyroid gland, as well as in the salivary glands.
J Pediatr Hematol Oncol
January 2025
Department of Pediatrics, The University of North Carolina at Chapel Hill, Chapel Hill, NC.
Constitutional platelet disorders have become better understood since Bernard and Soulier first described a case in 1948. Their diagnosis can also be challenging due to overlap in clinical presentation and lab findings with platelet type von Willebrand. Bernard-Soulier syndrome is a disorder caused by GPIb receptor mutations that decrease its affinity for von Willebrand factor resulting in reduced platelet function and macrothrombocytopenia.
View Article and Find Full Text PDFJ Biol Chem
December 2024
Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, USA. Electronic address:
Human genetic disorders are often caused by mutations of compound heterozygosity, where each allele of the mutant gene harbors a different genetic lesion. However, studies of such mutations are hampered due to the lack of an appropriate model. Here we describe a kinetic model of compound heterozygous variants in an obligate enzyme dimer that contains one mutation in one monomer and the other mutation in the second monomer.
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