BACKGROUND & AIMS: :Retinoblastoma (RB) is a childhood cancer developing in the retina due to RB1 pathologic variant. Herein we are evaluating the oncogenic mutations in the RB1 gene and the inheritance patterns of RB in the Jordanian patients. In this prospective study, the peripheral blood of 50 retinoblastoma patients was collected, genomic DNA was extracted, mutations were identified using Quantitative multiplex PCR (QM-PCR), Allele-specific PCR, Next Generation Sequencing analysis, and Sanger sequencing. In this cohort of 50 patients, 20(40%) patients had unilateral RB and 30(60%) were males. Overall, 36(72%) patients had germline disease, 17(47%) of whom had the same RB1 pathologic variant detected in one of the parents (inherited disease). In the bilateral group, all (100%) patients had germline disease; 13(43%) of them had inherited mutation. In the unilateral group, 6(30%) had germline disease, 4(20%) of them had inherited mutation. Nonsense mutation generating a stop codon and producing a truncated non-functional protein was the most frequent detected type of mutations (n = 15/36, 42%). Only one (2%) of the patients had mosaic mutation, and of the 17 inherited cases, 16(94%) had an unaffected carrier parent. In conclusion, in addition to all bilateral RB patients in our cohort, 30% of unilateral cases showed germline mutation. Almost half (47%) of germline cases had inherited disease from affected (6%) parent or unaffected carrier (94%). Therefore molecular screening is critical for the genetic counseling regarding the risk for inherited RB in both unilateral and bilateral cases including those with no family history.

背景与目标： ：视网膜母细胞瘤（RB）是由于RB1病理变异而在视网膜中发展的儿童期癌症。在这里，我们正在评估约旦患者中RB1基因的致癌突变和RB的遗传模式。在这项前瞻性研究中，收集了50例视网膜母细胞瘤患者的外周血，提取了基因组DNA，并使用定量多重PCR（QM-PCR），等位基因特异性PCR，下一代测序分析和Sanger测序鉴定了突变。在这50名患者中，单侧RB的患者为20（40％），男性为30（60％）。总体而言，有36名（72％）患者患有种系疾病，其中17名（47％）的父母之一（遗传病）患有相同的RB1病理变异。在双侧组中，所有（100％）患者都患有种系疾病。其中13（43％）人具有遗传突变。在单侧组中，有6个（30％）患有种系疾病，其中4个（20％）具有遗传突变。产生终止密码子并产生截短的非功能蛋白的无义突变是检测到的最常见突变类型（n = 15/36，42％）。只有一名（2％）患者患有花叶病突变，在17例遗传病例中，有16名（94％）患者的父母携带者未受影响。总之，除了我们队列中的所有双侧RB患者外，还有30％的单侧病例显示出种系突变。几乎一半（47％）的种系病例已从受影响的父母（6％）或未受影响的携带者（94％）遗传了疾病。因此，分子筛查对于单侧和双侧病例（包括无家族史的病例）中遗传性RB风险的遗传咨询至关重要。

BACKGROUND & AIMS: :A number of DNA probes from the short arm of the X chromosome have been used to study the inheritance of the translocation chromosomes in a girl with an X; autosome translocation and muscular dystrophy. The two translocation chromosomes were found to be derived from the father's single normal X chromosome, ruling out maternal inheritance of a pre-existent mutation and enhancing the concept that the de novo translocation is responsible for the dystrophic phenotype.

背景与目标： ：许多来自X染色体短臂的DNA探针已用于研究X染色体女孩的易位染色体的遗传；常染色体易位和肌肉营养不良。发现这两个易位染色体来源于父亲的单个正常X染色体，排除了母体先前存在的突变的遗传，并增强了从头易位导致营养不良表型的概念。

BACKGROUND & AIMS: :A study is described of the influence of the introduction of a dominant nuclear restorer gene into a cytoplasmic gynodioecious plant population. This study includes the consideration of separate effects on the relative female fertility of nuclear, cytoplasmic and sex (phenotypic) factors. Under these assumptions, the introduction of a dominant nuclear restorer gene into a cytoplasmic gynodioecious population can lead to several different situations: persistence of cytoplasmic gynodioecy, appearance of a nuclear-cytoplasmic gynodioecy, appearance of a nuclear gynodioecy or complete restoration of male fertility. The development of stable nuclear-cytoplasmic gynodioecy in a mathematical model is new and is possible because of the consideration of the separate relative female fertilities. The possibility of a transformation of cytoplasmic gynodioecy into a nuclear one has never been obtained before. It could constitute a route for the appearance of this latter kind of gynodioecy in plant populations. Finally, the possibilities of evolution of gynodioecy from one kind to the other, and towards dioecy, are discussed, as are some theoretical schemes that seem to correspond to observed actual situations.

背景与目标： ：一项研究描述了将显性核恢复基因导入细胞质雌雄异体植物种群的影响。这项研究包括对核，细胞质和性别（表型）因素对女性相对生育力的单独影响的考虑。在这些假设下，将显性核恢复基因导入细胞质雌雄异体种群可导致几种不同情况：细胞质雌雄同体的持续存在，核质雌雄同体的出现，核雌雄同体的出现或雄性生育力的完全恢复。在数学模型中开发稳定的核胞质生殖器是新的，并且由于考虑到单独的相对雌性受精而可能发展。以前从未获得过将细胞质雌雄激素转换成核的可能性。它可能构成在植物种群中出现这种后一种雌雄同体的途径。最后，讨论了雌雄同体从一种进化到另一种雌雄同体的可能性，以及一些似乎与观察到的实际情况相对应的理论方案。

BACKGROUND & AIMS: :Six genic mutations restricting clones to mating type VII (O) were isolated in syngen 4, Paramecium aurelia. The only three extensively tested were neither allelic nor closely linked. A second type of mutation, allelic to one of the O restricted mutants, was also found. Clones homozygous for this mutant gene were selfers, producing both O and E (VIII) mating types, but only when they were progeny of mating type E parental clones. While all seven mutant genes behaved as recessives in monohybrid crosses, clones heterozygous at two different loci often demonstrated an unanticipated phenotype: selfing. The significance of the findings is discussed in relation to mating type determination and the evolution of mating type systems.

背景与目标： ：在同源4，金黄色草履虫中分离出限制克隆到交配型VII（O）的六个基因突变。仅进行了广泛测试的三个基因既不是等位基因，也不是紧密相关的。还发现了第二种类型的突变，等位于O个限制性突变体之一。该突变基因纯合的克隆是自交体，产生O和E（VIII）交配类型，但仅当它们是E型交配亲本克隆的后代时才如此。尽管所有七个突变基因在单杂交杂交中均表现为隐性，但在两个不同基因座杂合的克隆通常表现出意料之外的表型：自交。讨论的结果的意义有关交配类型确定和交配类型系统的演变进行了讨论。

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BACKGROUND & AIMS: BACKGROUND:Klippel-Feil syndrome (KFS) represents a rare anomaly characterized by congenital fusion of the cervical vertebrae. The underlying molecular etiology remains largely unknown because of the genetic and phenotypic heterogeneity. METHODS:We consecutively recruited a Chinese cohort of 37 patients with KFS. The clinical manifestations and radiological assessments were analyzed and whole-exome sequencing (WES) was performed. Additionally, rare variants in KFS cases and controls were compared using genetic burden analysis. RESULTS:We primarily examined rare variants in five reported genes (GDF6, MEOX1, GDF3, MYO18B and RIPPLY2) associated with KFS and detected three variants of uncertain significance in MYO18B. Based on rare variant burden analysis of 96 candidate genes related to vertebral segmentation defects, we identified BAZ1B as having the highest probability of association with KFS, followed by FREM2, SUFU, VANGL1 and KMT2D. In addition, seven patients were proposed to show potential oligogenic inheritance involving more than one variants in candidate genes, the frequency of which was significantly higher than that in the in-house controls. CONCLUSIONS:Our study presents an exome-sequenced cohort and identifies five novel genes potentially associated with KFS, extending the spectrum of known mutations contributing to this syndrome. Furthermore, the genetic burden analysis provides further evidence for potential oligogenic inheritance of KFS.

背景与目标： 背景：Klippel-Feil综合征（KFS）代表一种罕见的异常，其特征是先天性颈椎融合。由于遗传和表型的异质性，潜在的分子病因仍是未知之数。
方法：我们连续招募了37例KFS患者的中国队列。分析了临床表现和放射学评估，并进行了全外显子测序（WES）。此外，使用遗传负担分析比较了KFS病例和对照中的罕见变异。
结果：我们主要检查了与KFS相关的五个报告基因（GDF6，MEOX1，GDF3，MYO18B和RIPPLY2）中的稀有变异体，并检测到MYO18B中三个具有不确定意义的变异体。基于对与椎骨节段缺陷相关的96个候选基因的罕见变异负荷分析，我们确定BAZ1B与KFS关联的可能性最高，其次是FREM2，SUFU，VANGL1和KMT2D。此外，提议了7名患者表现出潜在的寡聚遗传，涉及候选基因中的一种以上变异，其发生频率显着高于内部对照中的变异。
结论：我们的研究提出了一个外显子组测序队列，并鉴定了可能与KFS相关的五个新基因，从而扩展了导致该综合征的已知突变的范围。此外，遗传负担分析为KFS的潜在寡聚遗传提供了进一步的证据。

BACKGROUND & AIMS: :Persistent hyperplastic primary vitreous (PHPV) is an idiopathic congenital malformation confined to the eye that has no obvious cause and that is usually unilateral and sporadic. The clinical features of the classic PHPV syndrome include white, vascularized tissue covering some or all of the posterior surface of the lens; centrally dragged ciliary processes; secondary glaucoma caused by swelling of the lens or caused by contracture of the retrolental tissue, with anterior shifting of the lens-iris diaphragm; extensive intravitrael hemorrhaging; persistence of the hyaloid artery; and occasionally retinal detachment. In the present study we describe a patient with bilateral PHPV not associated with other diseases. Normal developmental milestones were reported. Family pedigree analysis revealed a similarly affected father, grandfather, 2 aunts, 1 paternal uncle and a grand uncle with 2 affected daughters. On examination the height, weight and skull circumference were on the 5th percentile. Bilateral B&A eye scan ultrasonography (B mode is two dimensional brightness mode ultrasonography, while A mode is one dimensional where echoes are represented by spikes of variable amplitude and timing) of both the patient and the father revealed a picture suggestive of persistent hyperplastic primary vitreous. Cytogenetics study by conventional culture technique using the CTG banding technique revealed a normal male karyotype 46, XY for both of them. Review of the London Dysmorphology Data Base (LDDB), OMIM, and recent medical literature revealed that this case to our knowledge represents the second report supporting autosomal dominant inheritance of PHPV not associated with other anomalies.

背景与目标： 永久性原发性玻璃体增生症（PHPV）是一种特发性先天性畸形，局限于眼睛，无明显原因，通常为单侧和散发性。经典的PHPV综合征的临床特征包括覆盖白色或部分晶状体后表面的白色血管组织。集中拖拉睫状过程；由晶状体肿胀或由后突组织挛缩引起的继发性青光眼，晶状体-虹膜隔膜前移；大量玻璃体内出血；舌骨动脉的持续性;偶尔视网膜脱离。在本研究中，我们描述了双侧PHPV与其他疾病无关的患者。报告了正常的发展里程碑。家庭血统分析显示，父亲，祖父，2个阿姨，1个父亲叔叔和1个有2个受影响女儿的祖父也受到同样的影响。经检查，身高，体重和颅骨围在第5个百分点。患者和父亲的双侧B＆A眼部扫描超声检查（B模式是二维亮度模式超声检查，而A模式是一维，其中回声由可变幅度和定时的尖峰表示），显示出提示持续性增生性原发性玻璃体的图像。通过常规培养技术使用CTG显带技术进行细胞遗传学研究，发现两者均具有正常的男性核型46，XY。对伦敦变形形态数据库（LDDB），OMIM和最新医学文献的审查显示，据我们所知，此病例代表了第二个支持PHPV的常染色体显性遗传而不与其他异常相关的报告。

BACKGROUND & AIMS: :Certain long-distance migratory animals, such as salmon and sea turtles, are thought to imprint on the magnetic field of their natal area and to use this information to help them return as adults. Despite a growing body of indirect support for such imprinting, direct experimental evidence thereof remains elusive. Here, using the fruit fly as a magnetoreceptive model organism, we demonstrate that exposure to a specific geographic magnetic field during a critical period of early development affected responses to a matching magnetic field gradient later in life. Specifically, hungry flies that had imprinted on a specific magnetic field from 1 of 3 widely separated geographic locations responded to the imprinted field, but not other magnetic fields, by moving downward, a geotactic behavior associated with foraging. This same behavior occurred spontaneously in the progeny of the next generation: female progeny moved downward in response to the field on which their parents had imprinted, whereas male progeny did so only in the presence of these females. These results represent experimental evidence that organisms can learn and remember a magnetic field to which they were exposed during a critical period of development. Although the function of the behavior is not known, one possibility is that imprinting on the magnetic field of a natal area assists flies and their offspring in recognizing locations likely to be favorable for foraging and reproduction.

背景与目标： ：某些远距离迁徙动物，例如鲑鱼和海龟，被认为会印在其出生地的磁场上，并利用这些信息帮助它们成年后返回。尽管越来越多的人间接支持这种压印，但其直接实验证据仍然难以捉摸。在这里，我们使用果蝇作为磁感受模型生物，证明了在早期发育的关键时期暴露于特定的地理磁场会影响生命后期对匹配的磁场梯度的响应。具体而言，已经从3个相距较远的地理位置中的1个上烙印在特定磁场上的饥饿的苍蝇通过向下移动来响应与该觅食相关的地势行为，从而对烙印的磁场做出了响应，但对其他磁场没有响应。相同的行为在下一代的子代中自发发生：雌性子代响应其父母的足迹而向下移动，而雄性子代只有在这些雌性的存在下才这样做。这些结果代表了实验证据，表明生物体可以学习和记住在关键的发育时期所暴露于的磁场。尽管行为的功能尚不清楚，但一种可能性是，在出生区域的磁场上留下印记有助于苍蝇及其后代识别可能有利于觅食和繁殖的位置。

BACKGROUND & AIMS: :Cutaneous malignant melanoma in Sinclair swine is a hereditary disease that develops in utero or during the first 6 weeks of life. In many cases, the tumors regress and piglets survive the disease. Two different sets of gene(s) might be involved in the disease: tumor initiator (suppressor) locus or loci and loci affecting the aggressiveness of the disease (number and stage of tumors). We develop maximum-likelihood methods for interval mapping for both types of loci. The experimental design consisted of a boar mated to tumor-bearing sows with recording of tumor status and number of tumors in the 6 weeks of life of the offspring. The model to search for the tumor initiator locus (with alleles T and t) was tested by computer simulation. Estimates of penetrances (Psi(TT) and Psi(Tt) for genotypes TT and Tt, respectively) were accurate even for small family sizes. Statistical power was >99% for a family size of 70 with Psi(TT) = 1 and Psi(Tt) = 0. The models to test for number of tumors incorporated genotype information for the tumor initiator locus. All models were tested with data from a single boar family of 72 piglets over swine chromosomes 6 and 8 (SSC6 and SSC8). No tumor evidence for initiator loci was found associated with these chromosomes. However, association of a QTL affecting number of tumors at birth near microsatellite SW1953 on SSC8 was chromosomewise significant (P<0.0124).

背景与目标： ：辛克莱猪的慢性恶性黑色素瘤是一种遗传性疾病，会在子宫内或生命的前6周内发展。在许多情况下，肿瘤消退，仔猪在疾病中幸存下来。该疾病可能涉及两套不同的基因：肿瘤引发剂（抑制子）基因座或基因座，以及影响疾病侵袭性（肿瘤的数量和阶段）的基因座。我们为两种基因座的区间作图开发了最大似然法。实验设计包括一个与带有肿瘤的母猪交配的公猪，并记录后代6周内的肿瘤状态和肿瘤数量。通过计算机模拟测试了用于寻找肿瘤引发剂基因座（具有等位基因T和t）的模型。外显率的估计（基因型TT和Tt分别为Psi（TT）和Psi（Tt））即使对于小型家庭来说也很准确。对于Psi（TT）= 1和Psi（Tt）= 0的70个家庭，统计功效> 99％。用于测试肿瘤数量的模型并入了肿瘤起始基因位点的基因型信息。所有模型均使用来自猪的第6和8号染色体（SSC6和SSC8）的72个仔猪的单个公猪家族的数据进行了测试。没有发现与这些染色体相关的起始位点的肿瘤证据。但是，影响SSC8上微卫星SW1953附近出生时肿瘤数量的QTL的关联在染色体上是显着的（P <0.0124）。