Mendelian Pattern Research Articles

The present situation of colorectal cancer in Chile

Colorectal (CRC) is one of the most common types of cancer worldwide. Most tumors develop from an adenoma in a period of 10 to 15 years, but some may appear without previous adenomatous lesions. Seventy-five percent of colorectal cancers are sporadic, 20% have a family component (first or second-degree relatives with CRC) and 5% have a hereditary predisposition with a Mendelian pattern. The epidemiological evolution in the recent years in Chile has a worrisome evolution and the treatment costs of advanced stages are a burden for the healthcare system. We herein highlight the main Chilean medical and scientific contributions on the pathogenesis, early diagnosis, and treatment of CRC, which lead to its better understanding, and therefore better management, based on local evidence.

Arrhythmogenic Cardiomyopathy: Molecular Insights for Improved Therapeutic Design.

Arrhythmogenic cardiomyopathy (ACM) is an inherited disorder characterized by structural and electrical cardiac abnormalities, including myocardial fibro-fatty replacement. Its pathological ventricular substrate predisposes subjects to an increased risk of sudden cardiac death (SCD). ACM is a notorious cause of SCD in young athletes, and exercise has been documented to accelerate its progression. Although the genetic culprits are not exclusively limited to the intercalated disc, the majority of ACM-linked variants reside within desmosomal genes and are transmitted via Mendelian inheritance patterns; however, penetrance is highly variable. Its natural history features an initial “concealed phase” that results in patients being vulnerable to malignant arrhythmias prior to the onset of structural changes. Lack of effective therapies that target its pathophysiology renders management of patients challenging due to its progressive nature, and has highlighted a critical need to improve our understanding of its underlying mechanistic basis. In vitro and in vivo studies have begun to unravel the molecular consequences associated with disease causing variants, including altered Wnt/β-catenin signaling. Characterization of ACM mouse models has facilitated the evaluation of new therapeutic approaches. Improved molecular insight into the condition promises to usher in novel forms of therapy that will lead to improved care at the clinical bedside.

Individual response of humans to ionising radiation: governing factors and importance for radiological protection

Tissue reactions and stochastic effects after exposure to ionising radiation are variable between individuals but the factors and mechanisms governing individual responses are not well understood. Individual responses can be measured at different levels of biological organization and using different endpoints following varying doses of radiation, including: cancers, non-cancer diseases and mortality in the whole organism; normal tissue reactions after exposures; and, cellular endpoints such as chromosomal damage and molecular alterations. There is no doubt that many factors influence the responses of people to radiation to different degrees. In addition to the obvious general factors of radiation quality, dose, dose rate and the tissue (sub)volume irradiated, recognized and potential determining factors include age, sex, life style (e.g., smoking, diet, possibly body mass index), environmental factors, genetics and epigenetics, stochastic distribution of cellular events, and systemic comorbidities such as diabetes or viral infections. Genetic factors are commonly thought to be a substantial contributor to individual response to radiation. Apart from a small number of rare monogenic diseases such as ataxia telangiectasia, the inheritance of an abnormally responsive phenotype among a population of healthy individuals does not follow a classical Mendelian inheritance pattern. Rather it is considered to be a multi-factorial, complex trait.

Functionally Enigmatic Genes in Cancer: Using TCGA Data to Map the Limitations of Annotations

Cancer is a comparatively well-studied disease, yet despite decades of intense focus, we demonstrate here using data from The Cancer Genome Atlas that a substantial number of genes implicated in cancer are relatively poorly studied. Those genes will likely be missed by any data analysis pipeline, such as enrichment analysis, that depends exclusively on annotations for understanding biological function. There is no indication that the amount of research - indicated by number of publications - is correlated with any objective metric of gene significance. Moreover, these genes are not missing at random but reflect that our information about genes is gathered in a biased manner: poorly studied genes are more likely to be primate-specific and less likely to have a Mendelian inheritance pattern, and they tend to cluster in some biological processes and not others. While this likely reflects both technological limitations as well as the fact that well-known genes tend to gather more interest from the research community, in the absence of a concerted effort to study genes in an unbiased way, many genes (and biological processes) will remain opaque.

Digenic variations of human COL4A3 and COL4A4 genes result in early onset renal failure

Type IV collagen protein is formed by the interaction of α3. α4. α5 chains and is encoded by COL4A3, COL4A4 and COL4A5 genes located on the chromosome 2 and the X-chromosome. Pathogenic variations in these genes are reported to be associated with the Alport sydrome (OMIM#104200) and follow the three classic Mendelian inheritance patterns; i) autosomal recessive, ii) autosomal dominant and iii) X-linked inheritance. Recently, with the emergence of massively parallel sequencing, a digenic etiology of Alport syndrome has been postulated, characterized by hematuria, proteinuria, end stage renal disease and chronic kidney failure often accompanied by the sensorineural deafness. Here, we report on the case of an 18 months old girl with clinical features of early onset renal failure in absence of any known cause. Patient was investigated using targeted massively parallel sequencing which revealed two novel variants in COL4A3 and COL4A4 genes. The variants were confirmed with Sanger sequencing as de novo missense variations c.4145G > T (p.Gly1382Val) and c.2956C > T (p.Pro986Ser) in the COL4A3 and COL4A4 genes, respectively. The variants are neither reported in population databases like 1000 Genomes, ExAC, etc. nor in Clinvar and are predicted to be disease causing by mutation prediction software. The HMM-based haplotype phasing revealed that the digenic variations identified are likely to be in cis. Overall, the findings suggest that the potential variants identified may explain the disease phenotype of the patient.

Inheritance of plumage morphs in Little Eagles Hieraaetus morphnoides in northern New South Wales

Polymorphism and inheritance of plumage colour in the Little Eagle Hieraaetus morphnoides were studied in northern New South Wales, by tallying records of parental morph combinations in breeding pairs and the morphs of their offspring in the 1980s, 2000s and 2017–2019 ( n = 41 pair combinations). The average ratio in breeding adults was 4.9 light:1 dark, with dark males outnumbering dark females (1.8:1). Light × light pairs always produced light young ( n = 32). Dark male × light female pairs variously produced light and dark offspring of both sexes ( n = 12). Light male × dark female pairs produced dark young of either sex ( n = 4) and one light young of unknown sex. One dark × dark pair produced a dark young. We conclude a Mendelian inheritance pattern with the dark morph recessive. From a small sample of mixed pairs with a dark male, the ratio of offspring morphs did not differ significantly from that expected by the Hardy–Weinberg equation, but mixed pairs with a light male produced 4 dark offspring to one light, versus the expected Hard –Weinberg ratio of 1.95 light: 1 dark. This outcome suggests a non-random transmission of the dark allele by heterozygous light males, and a similar pattern of inheritance to that in the related Booted Eagle H. pennatus .

Are Footedness and Lateral Postures Better Predictors of Hemispheric Dominance Than Handedness: A Cross-sectional Questionnaire-Based Clinical and Pedigree Study.

Objective Approximately 9 out of 10 individuals show right-hand dominance. The remaining 10% include left-hand dominant and mixed handed/ambidextrous individuals. Laterality, lateral postures or lateral preference is defined by various authors as the most comfortable posture that an individual prefers to assume. The current study aims at finding the distribution of these lateral postures and their correlation with handedness/dominant side. Materials and Methods The study was done in medical and nursing students in the age group 18 to 22 years. The patients were asked to fill a self-assessment questionnaire to determine handedness and footedness. The laterality traits were observed by asking the patients to do by themselves after an untailored demonstration. Statistical Analysis The relationship between study parameters was assessed using Chi-square test. Pearson’s correlation test was done to assess the strength of association between comfort ratings of the various laterality postures. Results In our study, 96.5% were right handed and 79.9% of patients were right footed. Also, 50.8% preferred right-hand clasping, 53.9% preferred left-arm folding, and 60.6% preferred right-leg folding. A statistically significant correlation was seen between foot preference and lateral postures and arm folding and hand clasping (p < 0.05). A significant association was also found between handedness and positive history of retraining. Sidedness did not follow any Mendelian pattern of inheritance. Conclusions Handedness is affected by genetic and environmental factors. Since cultural and traditional practices can affect the lateral postures and handedness, it is important to know the relationship between laterality postures and sidedness and the impact of retraining on them. These postures are measures of cerebral dominance and are clinically important.

A novel FZD6 mutation revealed the cause of cleft lip and/or palate in a Chinese family

Cleft lip and/or palate (CL/P) is a most common craniofacial birth defect which has multifactorial etiology. In our study, we aimed to discover the underlying etiological gene variation in a Chinese family diagnosed as non-syndromic CL/P (NSCL/P). The blood sample of the proband and her parents were detected by whole exome sequencing. The Mendelian inheritance pattern, allele frequency, variation location, function analysis and literature search were applied to filtrate and screen the mutation. Besides, the candidates were confirmed by Sanger sequencing. We meanwhile explored the conservative analysis and protein homology simulation. As a result, a start-lost mutation c.1A > GAtg/Gtg in the Frizzled-6 (FZD6) gene predicting p.Met1 was detected. The variation has not been reported before and was predicted to be harmful. The alteration caused missing of two starting amino acids that are evolutionarily conserved for FZD6 protein. Moreover, the specific structure of the mutant protein obviously changed according to the results of the homologous model. In conclusion, the results suggest c.1A > GAtg/Gtg in the FZD6 (NM_001164616) might be the genetic etiology for non-syndromic CL/P in this pedigree. Furthermore, this finding provided new etiologic information, supplementing the evidence that FZD6 is a strong potential gene for CL/P.

Effects of a male meiotic driver on male and female transcriptomes in the house mouse.

Not all genetic loci follow Mendel's rules, and the evolutionary consequences of this are not yet fully known. Genomic conflict involving multiple loci is a likely outcome, as restoration of Mendelian inheritance patterns will be selected for, and sexual conflict may also arise when sexes are differentially affected. Here, we investigate effects of the t haplotype, an autosomal male meiotic driver in house mice, on genome-wide gene expression patterns in males and females. We analysed gonads, liver and brain in adult same-sex sibling pairs differing in genotype, allowing us to identify t-associated differences in gene regulation. In testes, only 40% of differentially expressed genes mapped to the approximately 708 annotated genes comprising the t haplotype. Thus, much of the activity of the t haplotype occurs in trans, and as upregulation. Sperm maturation functions were enriched among both cis and trans acting t haplotype genes. Within the t haplotype, we observed more downregulation and differential exon usage. In ovaries, liver and brain, the majority of expression differences mapped to the t haplotype, and were largely independent of the differences seen in the testis. Overall, we found widespread transcriptional effects of this male meiotic driver in the house mouse genome.

Theme 3 In vitro experimental models

Background: Ongoing disease gene discoveries continue to drive our understanding of the molecular and cellular mechanisms underlying ALS. Causative genes from 60% of ALS families have been identified using modern genetic techniques, but the causal gene defect is yet to be identified in the remaining 40% of families. These remaining families often do not follow true Mendelian inheritance patterns and are challenging to solve using traditional genetic analysis alone. In vitro and in vivo studies have become critical in assessing and validating these ALS candidate genes.Objectives: In this study, we aim to develop and validate the utility of an in vitro functional pipeline for the discovery and validation of novel ALS candidate genes.Methods: A panel of cell based-assays were applied to candidate genes to examine the presence/absence of known ALS pathologies in cell lines as well as human autopsy tissues. These include immunofluorescence, flow cytometry and western blotting to study toxicity, neuronal inclusion formation, interaction with TDP-43, aberrant protein degradation and accumulation in detergent-insoluble cellular fractions. Immunohistochemistry and immunofluorescence were also used to examine if candidates were present in neuronal inclusions from ALS patient spinal cord tissues.Results: The in vitro pipeline was applied to five candidate genes from an ALS family that is negative for known ALS gene mutations. Two candidates were prioritized as top candidates based on their capacity to induce known ALS cellular pathologies. In transfected cells, the variants in these two genes caused a significantly higher toxicity than wild type, formed detergent insoluble inclusions and was able to co-aggregate with TDP-43 in neuronal cells. The variants have also led to protein degradation defects. One of the candidates also co-localised with TDP-43-positive neuronal inclusions in sporadic ALS patient post-mortem tissues, a signature pathology of ALS.Discussion and conclusions: We have demonstrated the utility of a functional prioritization pipeline and successfully prioritized two novel candidate ALS genes. These genes, and its associated pathways, will be further investigated through the development of animal models to establish if there is support for its role in ALS. New ALS genes offer fresh diagnostic and therapeutic targets and tools for the generation of novel animal models to better understand disease biology and offer preclinical testing of candidate treatments for ALS in the future.

Improving the phenotype risk score as a scalable approach to identifying patients with Mendelian disease.

The Phenotype Risk Score (PheRS) is a method to detect Mendelian disease patterns using phenotypes from the electronic health record (EHR). We compared the performance of different approaches mapping EHR phenotypes to Mendelian disease features. PheRS utilizes Mendelian diseases descriptions annotated with Human Phenotype Ontology (HPO) terms. In previous work, we presented a map linking phecodes (based on International Classification of Diseases [ICD]-Ninth Revision) to HPO terms. For this study, we integrated ICD-Tenth Revision codes and lab data. We also created a new map between HPO terms using customized groupings of ICD codes. We compared the performance with cases and controls for 16 Mendelian diseases using 2.5 million de-identified medical records. PheRS effectively distinguished cases from controls for all 15 positive controls and all approaches tested (P < 4 × 1016). Adding lab data led to a statistically significant improvement for 4 of 14 diseases. The custom ICD groupings improved specificity, leading to an average 8% increase for precision at 100 (-2% to 22%). Eight of 10 adults with cystic fibrosis tested had PheRS in the 95th percentile prio to diagnosis. Both phecodes and custom ICD groupings were able to detect differences between affected cases and controls at the population level. The ICD map showed better precision for the highest scoring individuals. Adding lab data improved performance at detecting population-level differences. PheRS is a scalable method to study Mendelian disease at the population level using electronic health record data and can potentially be used to find patients with undiagnosed Mendelian disease.

Whole genome sequencing and rare variant analysis in essential tremor families.

Essential tremor (ET) is one of the most common movement disorders. The etiology of ET remains largely unexplained. Whole genome sequencing (WGS) is likely to be of value in understanding a large proportion of ET with Mendelian and complex disease inheritance patterns. In ET families with Mendelian inheritance patterns, WGS may lead to gene identification where WES analysis failed to identify the causative single nucleotide variant (SNV) or indel due to incomplete coverage of the entire coding region of the genome, in addition to accurate detection of larger structural variants (SVs) and copy number variants (CNVs). Alternatively, in ET families with complex disease inheritance patterns with gene x gene and gene x environment interactions enrichment of functional rare coding and non-coding variants may explain the heritability of ET. We performed WGS in eight ET families (n = 40 individuals) enrolled in the Family Study of Essential Tremor. The analysis included filtering WGS data based on allele frequency in population databases, rare SNV and indel classification and association testing using the Mixed-Model Kernel Based Adaptive Cluster (MM-KBAC) test. A separate analysis of rare SV and CNVs segregating within ET families was also performed. Prioritization of candidate genes identified within families was performed using phenolyzer. WGS analysis identified candidate genes for ET in 5/8 (62.5%) of the families analyzed. WES analysis in a subset of these families in our previously published study failed to identify candidate genes. In one family, we identified a deleterious and damaging variant (c.1367G>A, p.(Arg456Gln)) in the candidate gene, CACNA1G, which encodes the pore forming subunit of T-type Ca(2+) channels, CaV3.1, and is expressed in various motor pathways and has been previously implicated in neuronal autorhythmicity and ET. Other candidate genes identified include SLIT3 which encodes an axon guidance molecule and in three families, phenolyzer prioritized genes that are associated with hereditary neuropathies (family A, KARS, family B, KIF5A and family F, NTRK1). Functional studies of CACNA1G and SLIT3 suggest a role for these genes in ET disease pathogenesis.

An Introduction to Clinical Genetics

Understanding the principles of basic genetics is the beginning of understanding more complex and advanced genetic studies, such as epigenetics. This article presents a review of the basic concepts of genetics, Mendelian and non-Mendelian patterns of inheritance, and basic genetic testing.

Multi gene panel testing for hereditary breast cancer - is it ready to be used?

Breast cancer is one of the most common malignancies and the leading cause of death among women worldwide. About 20% of breast cancers are hereditary. Approximately 30% of the mutations have remained negative after testing BRCA1/2 even in families with a Mendelian inheritance pattern for breast cancer. Additional non-BRCA genes have been identified as predisposing for breast cancer. Multi gene panel testing tries to cover and explain the BRCA negative inherited breast cancer, improving efficiency, speed and costs of the breast cancer screening.We identified 23 studies reporting results from individuals who have undergone multi gene panel testing for hereditary breast cancer and noticed a prevalence of 1–12% of non-BRCA genes, but also a high level of variants of uncertain significance.A result with a high level of variants of uncertain significance is likely to be more costly than bring benefits, as well as increase the anxiety for patients. Regarding further development of multi gene panel testing, more research is required to establish both the optimal care of patients with cancer (specific treatments like PARP inhibitors) and the management of unaffected individuals (chemoprevention and/or prophylactic surgeries). Early detection in these patients as well as prophylactic measures will significantly increase the chance of survival. Therefore, multi gene panel testing is not yet ready to be used outside clear guidelines. In conclusion, studies on additional cohorts will be needed to better define the real prevalence, penetrance and the variants of these genes, as well as to describe clear evidence-based guidelines for these patients.

Macrophage migration inhibitory factor polymorphism (rs755622) in alopecia areata: a possible role in disease prevention.

Alopecia areata (AA) is an organ-specific autoimmune disease that targets the bulb of the hair follicles and results in non-scarring hair loss that can range from patchy lesions to involvement of the entire scalp. AA develops when the hair follicles lose their physiologic state of immune privilege. One of the key factors that help in maintaining this immune privilege by suppressing natural killer cells is macrophage migration inhibitory factor (MIF). Surprisingly, MIF is also known to provoke autoimmunity by upregulating cytokines. To address this dilemma and understand the exact nature of the involvement of MIF in disease pathogenesis we investigated the association of MIF gene polymorphisms (-173 G > C, rs755622) with AA by conducting a case-control study of 274 subjects. We observed that the frequency of the C allele in the patients was significantly lower than the control group (0.15, 0.23, respectively, p = 0.01) and the combined frequencies of the CC and GC genotypes (dominant Mendelian pattern) had the most prevalent difference between the two groups (odds ratio 0.60, 95% confidence interval 0.36-0.99; p = 0.048).Since the C allele is associated with higher MIF transcription levels, this could infer that MIF is more likely to attribute to the preservation of the immune privilege rather than acting as a proinflammatory factor.

MON-539 Mice Harboring a Germline Heterozygous AP2S1 Mutation, Arg15Leu, Are a Model for Familial Hypocalciuric Hypercalcemia Type 3 (FHH3)

Familial hypocalciuric hypercalcemia (FHH) is a disorder of calcium homeostasis comprising three reported genetic variants: FHH types 1 and 2 are due to germline loss-of-function mutations of the calcium-sensing receptor (CaSR) and G-protein subunit α-11 (Gα11), respectively, whereas, FHH type 3 (FHH3) is mainly caused by germline heterozygous loss-of-function mutations affecting the Arg15 residue (Arg15Cys, Arg15His or Arg15Leu) of the adaptor-related protein complex 2-sigma subunit (AP2σ), which is encoded by the AP2S1 gene, and regulates CaSR endocytosis and endosomal signaling. FHH is considered to be an asymptomatic disorder characterised by mild-to-moderate hypercalcemia, normal or mildly elevated parathyroid hormone (PTH) concentrations and low urinary calcium excretion. However, some FHH3 patients, especially those harboring the Arg15Leu AP2S1 mutation, have marked and symptomatic hypercalcemia, thereby indicating that FHH3 may represent a more severe clinical disorder. To further evaluate the impact of the Arg15Leu AP2S1 mutation on calcium homeostasis, we utilised CRISPR/Cas9-mediated gene editing to generate C57BL/6J mice harboring the germline Arg15Leu mutation. Plasma and 24-hour urine samples were collected for biochemical analysis, and bone mineral density (BMD) was measured by dual energy X-ray absorptiometry (DEXA). All studies were conducted in mice aged 12-15 weeks (n = 10-12 mice per genotype), and in accordance with institutional welfare guidelines. Wild-type (Ap2s1+/+), heterozygous (Ap2s1+/L15) and homozygous (Ap2s1L15/L15) mice were born as expected for a Mendelian pattern of inheritance, however, Ap2s1L15/L15 mice died within 48 hours of birth. In contrast, male and female Ap2s1+/L15mice were viable and biochemical analysis showed marked hypercalcemia (plasma albumin-adjusted calcium = 2.77±0.02 mmol/L) compared to wild-type (WT) mice (plasma albumin-adjusted calcium = 2.13±0.03 mmol/L, p<0.0001), and this finding was associated with significant hypophosphatemia and hypermagnesemia. Male and female Ap2s1+/L15mice also had significant elevations of plasma PTH (157±14 pmol/L) compared to WT mice (63±10 pmol/L, p<0.0001). Furthermore, urine analysis showed that Ap2s1+/L15mice were significantly hypocalciuric (fractional excretion of calcium (FECa) = 0.016±0.002) compared to WT mice (FECa =0.029±0.002, p<0.01), whilst, DEXA analysis demonstrated that Ap2s1+/L15mice have significantly reduced BMD. Thus, these studies have established a mouse model for FHH3, which highlights the importance of the AP2σ protein in the parathyroid and renal regulation of mineral and bone homeostasis. In addition, these findings demonstrate that the germline heterozygous Arg15Leu AP2S1 mutation causes a severe form of FHH characterized by marked hypercalcemia, hyperparathyroidism and reduced BMD.

OR30-5 Germline Ablation of G-Protein Subunit Alpha-11 in Mice Causes Hypercalcemia That Is Rectified by Treatment with Cinacalcet

G-protein subunit α-11 (Gα11) is a signalling partner of the calcium-sensing receptor (CaSR), which is a G-protein coupled receptor that plays a major role in calcium homeostasis by regulating parathyroid hormone (PTH) secretion, urinary calcium excretion and skeletal development. Although loss-of-function point mutations of the GNA11 gene, which encodes Gα11, have been shown to increase plasma calcium concentrations and cause familial hypocalciuric hypercalcemia type 2 (FHH2), the overall contribution of Gα11 to the parathyroid, bone and renal regulation of calcium homeostasis remains to be established. The aim of this study was to characterise the impact of selective germline ablation of Gα11 on plasma concentrations of albumin-adjusted calcium (adj-calcium) and PTH, 24-hour urinary calcium excretion, and bone mineral density (BMD) in adult male and female heterozygous and homozygous Gna11 null C57BL/6N mice (n=13-16 mice per genotype), which had been previously generated by the International Mouse Phenotyping Consortium (IMPC). These mice were also treated with cinacalcet to assess whether this CaSR positive allosteric modulator can rectify any alterations in calcium homeostasis. All studies were conducted in accordance with institutional welfare guidelines. Male and female heterozygous Gna11 null (Gna11+/-) mice were viable and significantly hypercalcemic (plasma adj-calcium = 2.47±0.02 mM) compared to wild-type (WT) mice (plasma adj-calcium = 2.33±0.01 mM, p<0.0001). Gna11+/- mice showed no alterations in plasma PTH or 24-hour urinary calcium. In contrast, homozygous Gna11 null (Gna11-/-) mice showed reduced viability and the proportion of viable Gna11-/- mice was >25% less than would be expected from a Mendelian pattern of inheritance (p=0.01, Chi-squared analysis). Moreover, male and female Gna11-/- mice had significantly reduced body weight and were significantly more hypercalcemic (plasma adj-calcium = 2.70±0.02 mM) than Gna11+/- or WT mice (p<0.0001). Female Gna11-/- mice also showed significant increases in plasma PTH and 24-hour urinary calcium compared to female Gna11+/- and WT mice. However, no alterations in BMD were observed in male and female Gna11+/- or Gna11-/- mice. Administration of a single oral 30mg/kg cinacalcet dose significantly reduced plasma adj-calcium and PTH in Gna11+/- and Gna11-/- mice, and normalised plasma adj-calcium concentrations in Gna11-/- mice at 1-hour post-dose. Thus, these findings demonstrate that Gα11 plays a major role in regulating plasma calcium concentrations, but does not influence BMD, nor represent a key mediator of urinary calcium excretion. Furthermore, cinacalcet rectifies the hypercalcemia of Gna11 null mice, thus indicating that this CaSR-targeted compound may modulate parathyroid gland function in a Gα11-independent manner.

Colour plumage polymorphism in the Booted Eagle: inheritance pattern and temporal stability of the morph frequencies

AbstractColour polymorphism occurs in several animal taxa and in around 3.5% of bird species. This phenomenon is disproportionately high in raptors, affecting approximately 30% of species. However, there are only four research studies in wildAccipitridaespecies and two inFalconidaespecies on colour plumage polymorphism. Here, we used the data collected over 23 years (1995‐2017) for non‐tagged individuals of three Spanish Booted Eagle (Hieraaetus pennatus) populations in order to evaluate the stability of morph frequencies during the study period, also for each sex and between sexes, and also the inheritance pattern of colour plumage polymorphism. Our results showed that morph ratios appeared stable over time and between sexes. In one of the studied populations, we found a biased proportion between dark males and dark females, with very few dark males. Our results suggest that this species follows the typical Mendelian inheritance pattern, the light allele being dominant, for which we propose a system involving two loci with epistasis and two alleles per loci. This system would explain all the cases of colour morphs observed in our studied populations and also that described in the main raptor identification guides. Although our results showed no sex‐linked morph inheritance, the offspring produced in mixed pairs with light males and dark females appear significantly linked to the colour morph of the female with a ratio 1:1.49 light/dark, contrarily to the ratio of 4.35:1 predicted by the Hardy‐Weinberg equilibrium equation. This fact suggests a transmission ratio distortion (TRD) phenomenon in heterozygous light morph males. Further investigation using molecular genetic markers will be necessary to check the genotypes of breeding adults and their offspring to confirm the inheritance mechanisms operating in this species.

A Comparative Study of Dermatoglyphic Patterns of Fingers in Normal Children and In Children with Congenital Heart Diseases

Introduction: Dermatoglyphics is the study of epidermal ridges and their configurations on the palmar and the plantar regions. Currently dermatoglyphics is being used as a tool in the field of biology, anthropology, genetics and medicine to explain, compare and to predict the occurrence of bio medical events. Finger prints are usually categorized into three basic groups namely arches (60-65%), loops (30-35%) and whorls (5%). Any prenatal insult during this critical period of embryogenesis/organ system development should have an influence on the dermatoglyphic patterns.4Congenital heart defects are a heterogeneous group of diseases in which etiology, importance of genetic as well as environmental factors have been recognized. These defects show a familial tendency but no Mendelian pattern of inheritance has been described. In the present study, finger dermatoglyphic patterns in congenital heart diseases are studied and compared with controls. Subjects and methods: Dermatoglyphics are studied in 100 children with congenital heart diseases, both males and females. The dermatoglyphic patterns of palms and fingers were studied and the information was recorded systematically and statistically analyzed. Results: Ventricular septal defects (VSD) form the majority in the both the males (50%) and females (34.8%) in the congenital heart diseases group, followed by Atrial septal defects (ASD) in both males (20.4%) and females (39.1%). In both, the cases and controls group, it is found that the majority are loops followed by whorls and then the arches. The increase in whorls in congenital heart diseases is statistically significant with p value < 0.001. Comparing the cases with controls it is found that the Whorls (p < 0.001) and the loops (p <0.001) were statistically significant, it means that the Whorls are more frequently found in congenital heart diseases than the controls. Conclusion: Congenital heart diseases are associated with abnormal dermatoglyphic patterns. Increased number of Whorls and decreased number of Arches are seen in the congenital heart disease children. The above fingerprint pattren may help as a diagnostic aid in diagnosis of congenital heart diseases in children. They may also help in distinguishing congenital heart diseases from the functional and acquired heart diseases. A larger sample study is required to ascertain the value of this dermatoglyphic parameter as a diagnostic tool in congenital heart diseases in children.

Inheritance of coat colour in the cane Corso Italiano dog

BackgroundThe inheritance of different coat colours in the Cane Corso Italiano dog has not been described thus far. We analysed data from 23,271 dogs and bitches using the Cane Corso Italiano Pedigree Database. We are describing for the first time the coat colour segregation ratios in Cane Corso Italiano offspring arising from crosses between parents of all possible coat colour combinations.ResultsSegregation ratios that do not follow a Mendelian pattern suggest that additional genes are active in the determination of coat colour. Segregation ratios of offspring produced by parental crossing (male colour A x female colour B) were compared with the ratios of offspring produced by reciprocal crossing (male colour B x female colour A) in all possible coat colour combinations.Most of the segregation ratios were the same, but some segregation ratios in reciprocal crosses differed. This result suggests that at least one gene responsible for coat colour is located on a sex chromosome. The sex ratio was analysed in the offspring of all colour groups. A ratio of 1:1 was not confirmed in 8 colour groups by the chi-square test.ConclusionsWe described for the first time coat colour segregation ratios in Cane Corso Italiano dogs. Furthermore, we present the hypothesis that at least one gene responsible for coat colour is located on a sex chromosome.