Do partial AZFc deletions affect the sperm retrieval rate in non-mosaic Klinefelter patients undergoing microdissection testicular sperm extraction?

Background The purpose of this study is to evaluate the prognostic factors for sperm retrieval and determine if Y chromosome deletion is associated with deleterious effects. Whether Y chromosome deletion determines the sperm retrieval rate in non-mosaic Klinefelter patients has not yet been addressed. Methods We retrospectively collected medical records of azoospermic patients from Sep 2009 to Dec 2018, and enrolled 66 non-mosaic 47, XXY patients who were receiving mTESE. The predictive values of patients age, serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, prolactin, estradiol and Y chromosome deletion were assessed for successful sperm recovery. Results Testicular sperm recovery was successful in 24 (36.4%) of 66 men. The mean age (36.0 vs. 36.6 years), and levels of FSH (30.0 vs 36.9 IU/L), LH (17.7 vs 21.9 IU/L), testosterone (2.4 vs. 2.1 ng/ml), prolactin (9.1 vs. 8.8 ng/ml), and estradiol (19.4 vs. 22.3 pg/ml) did not show any significant difference when comparing patients with and without successful sperm retrieval. Partial deletion of azoospermic factor c (AZFc) was noted in 5 (20.8%) of 24 patients with successful sperm retrieval, including three b2/b3 and two gr/gr deletion cases, whereas 4 (9.5%) of 42 patients with unsuccessful sperm retrieval were noted to have AZFc partial deletion (one b2/b3 , one sY1206 and two gr/gr deletion), though the difference was not statistically significant (p=0.27) Conclusion According to present results, age and AZFc partial deletion status should not be a deterrent for azoospermic males with non-mosaic Klinefelter syndrome to undergo mTESE.

A partial pathogenicity chromosome in Fusarium oxysporum is sufficient to cause disease and can be horizontally transferred

During host colonization, plant pathogenic fungi secrete proteins, called effectors, to facilitate infection. Collectively, effectors may defeat the plant immune system, but usually not all effectors are equally important for infecting a particular host plant. In Fusarium oxysporum f.sp. lycopersici, all known effector genes – also called SIX genes – are located on a single accessory chromosome which is required for pathogenicity and can also be horizontally transferred to another strain. To narrow down the minimal region required for virulence, we selected partial pathogenicity chromosome deletion strains by fluorescence-assisted cell sorting of a strain in which the two arms of the pathogenicity chromosome were labelled with GFP and RFP, respectively. By testing the virulence of these deletion mutants, we show that the complete long arm and part of the short arm of the pathogenicity chromosome are not required for virulence. In addition, we demonstrate that smaller versions of the pathogenicity chromosome can also be transferred to a non-pathogenic strain and they are sufficient to turn the non-pathogen into a pathogen. Surprisingly, originally non-pathogenic strains that had received a smaller version of the pathogenicity chromosome were much more aggressive than recipients with a complete pathogenicity chromosome. Whole genome sequencing analysis revealed that partial deletions of the pathogenicity chromosome occurred mainly close to repeats, and that spontaneous duplication of sequences in accessory regions is frequent both in chromosome deletion strains and in horizontal transfer (recipient) strains.Author SummaryFungal genomes can often be divided into a core genome, which is essential for growth, and an accessory genome which is dispensable. The accessory genome in fungi can be beneficial under some conditions. For example, in some plant-pathogenic fungi, virulence genes are present in the accessory genome, which enable these fungi to cause disease on certain hosts. In Fusarium oxysporum f.sp. lycopersici, which infects tomato, all host-specific virulence genes are located on a single accessory chromosome. This ‘pathogenicity chromosome’ can be horizontally transferred between strains. Here, we found that many suspected virulence genes are in fact not required for virulence because strains without a large part of the pathogenicity chromosome, including these genes, showed no reduced virulence. In addition, we demonstrate that partial pathogenicity chromosomes can be horizontally transferred to a non-pathogen. Surprisingly, originally non-pathogenic strains that had received a partial pathogenicity chromosome were more virulent than strains that had received the complete pathogenicity chromosome.

Do partial AZFc deletions affect the sperm retrieval rate in non-mosaic Klinefelter patients undergoing microdissection testicular sperm extraction?

Background The purpose of this study is to evaluate the prognostic factors for sperm retrieval and determine if Y chromosome deletion is associated with deleterious effects. Whether Y chromosome deletion determines the sperm retrieval rate in non-mosaic Klinefelter patients has not yet been addressed.Methods We retrospectively collected medical records of azoospermic patients from Sep 2009 to Dec 2018, and enrolled 66 non-mosaic 47, XXY patients who were receiving mTESE. The predictive values of patients age, serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, prolactin, estradiol and Y chromosome deletion were assessed for successful sperm recovery.Results Testicular sperm recovery was successful in 24 (36.4%) of 66 men. The mean age (36.0 vs. 36.6 years), and levels of FSH (30.0 vs 36.9 IU/L), LH (17.7 vs 21.9 IU/L), testosterone (2.4 vs. 2.1 ng/ml), prolactin (9.1 vs. 8.8 ng/ml), and estradiol (19.4 vs. 22.3 pg/ml) did not show any significant difference when comparing patients with and without successful sperm retrieval. Partial deletion of azoospermic factor c (AZFc) was noted in 5 (20.8%) of 24 patients with successful sperm retrieval, including three b2/b3 and two gr/gr deletion cases, whereas 4 (9.5%) of 42 patients with unsuccessful sperm retrieval were noted to have AZFc partial deletion (one b2/b3 , one sY1206 and two gr/gr deletion), though the difference was not statistically significant (p=0.27)Conclusion According to present results, age and AZFc partial deletion status should not be a deterrent for azoospermic males with non-mosaic Klinefelter syndrome to undergo mTESE.

Programmed Chromosome Deletion in the Ciliate Oxytricha trifallax

The ciliate Oxytricha trifallax contains two nuclei: a germline micronucleus and a somatic macronucleus. These two nuclei diverge significantly in genomic structure. The micronucleus contains approximately 100 chromosomes of megabase scale, while the macronucleus contains 16,000 gene-sized, high ploidy “nanochromosomes.” During its sexual cycle, a copy of the zygotic germline micronucleus develops into a somatic macronucleus via DNA excision and rearrangement. The rearrangement process is guided by multiple RNA-based pathways that program the epigenetic inheritance of sequences in the parental macronucleus of the subsequent generation. Here, we show that the introduction of synthetic DNA molecules homologous to a complete native nanochromosome during the rearrangement process results in either loss or heavy copy number reduction of the targeted nanochromosome in the macronucleus of the subsequent generation. This phenomenon was tested on a variety of nanochromosomes with different micronuclear structures, with deletions resulting in all cases. Deletion of the targeted nanochromosome results in the loss of expression of the targeted genes, including gene knockout phenotypes that were phenocopied using alternative knockdown approaches. Further investigation of the chromosome deletion showed that, although the full length nanochromosome was lost, remnants of the targeted chromosome remain. We were also able to detect the presence of telomeres on these remnants. The chromosome deletions and remnants are epigenetically inherited when backcrossed to wild type strains, suggesting that an undiscovered mechanism programs DNA elimination and cytoplasmically transfers to both daughter cells during conjugation. Programmed deletion of targeted chromosomes provides a novel approach to investigate genome rearrangement and expands the available strategies for gene knockout in Oxytricha trifallax.

Chromosome Deletion 1q43q44: A Case Review

Numerous chromosome abnormalities are seen in NICUs around the world. With increased access to health care, in some cases, parents and practitioners are aware of an abnormality prior to birth, and a plan of care can be made. However, in many situations there is no prenatal diagnosis and these discoveries and diagnoses are made during the neonate's NICU stay. Providers in the NICU setting need to have a vast understanding of chromosome abnormalities, as they may be the first to guide parents through the maze of decisions that will follow. This case study analyzes a very rare deletion on chromosome 1q43q44. The 1q43q44 deletion is located at the subtelomeric region, the region farthest from the centromere, on the long arm of chromosome 1. This case study describes Baby D, who presented with multiple anomalies and was subsequently diagnosed with 1q43q44 deletion.