The Rosetta Phenotype Harmonization Method Facilitates Finding a Relationship Quantitative Trait Locus for a Complex Cognitive Trait.

Genetics researchers increasingly combine data across many sources to increase power and to conduct analyses that cross multiple individual studies. However, there is often a lack of alignment on outcome measures when the same constructs are examined across studies. This inhibits comparison across individual studies and may impact the findings from meta-analysis.

Structural Variations Contribute to the Genetic Etiology of Autism Spectrum Disorder and Language Impairments.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by restrictive interests and/or repetitive behaviors and deficits in social interaction and communication. ASD is a multifactorial disease with a complex polygenic genetic architecture. Its genetic contributing factors are not yet fully understood, especially large structural variations (SVs).

Common genetic risk factors in ASD and ADHD co-occurring families.

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are two major neurodevelopmental disorders that frequently co-occur. However, the genetic mechanism of the co-occurrence remains unclear. The New Jersey Language and Autism Genetics Study (NJLAGS) collected more than 100 families with at least one member affected by ASD.

MicroRNA and MicroRNA-Target Variants Associated with Autism Spectrum Disorder and Related Disorders.

Autism spectrum disorder (ASD) is a childhood neurodevelopmental disorder with a complex and heterogeneous genetic etiology. MicroRNA (miRNA), a class of small non-coding RNAs, could regulate ASD risk genes post-transcriptionally and affect broad molecular pathways related to ASD and associated disorders. Using whole-genome sequencing, we analyzed 272 samples in 73 families in the New Jersey Language and Autism Genetics Study (NJLAGS) cohort.

Autism NPCs from both idiopathic and CNV 16p11.2 deletion patients exhibit dysregulation of proliferation and mitogenic responses.

Neural precursor cell (NPC) dysfunction has been consistently implicated in autism. Induced pluripotent stem cell (iPSC)-derived NPCs from two autism groups (three idiopathic [I-ASD] and two 16p11.2 deletion [16pDel]) were used to investigate if proliferation is commonly disrupted.

Within-task variability on standardized language tests predicts autism spectrum disorder: a pilot study of the Response Dispersion Index.

Background: Qualitatively atypical language development characterized by non-sequential skill acquisition within a developmental domain, which has been called developmental deviance or difference, is a common characteristic of autism spectrum disorder (ASD). We developed the Response Dispersion Index (RDI), a measure of this phenomenon based on intra-subtest scatter of item responses on standardized psychometric assessments, to assess the within-task variability among individuals with language impairment (LI) and/or ASD.

Methods: Standard clinical assessments of language were administered to 502 individuals from the New Jersey Language and Autism Genetics Study (NJLAGS) cohort.

Social (Pragmatic) Communication Disorder: Another name for the Broad Autism Phenotype?

The ' (5th ed.) Social (Pragmatic) Communication Disorder is meant to capture the social elements of communication dysfunction in children who do not meet autism spectrum disorder criteria. It is unclear whether Social (Pragmatic) Communication Disorder captures these elements without overlapping with Autism Spectrum Disorder or the ' (5th ed.

Behavioral and Molecular Genetics of Reading-Related AM and FM Detection Thresholds.

Auditory detection thresholds for certain frequencies of both amplitude modulated (AM) and frequency modulated (FM) dynamic auditory stimuli are associated with reading in typically developing and dyslexic readers. We present the first behavioral and molecular genetic characterization of these two auditory traits. Two extant extended family datasets were given reading tasks and psychoacoustic tasks to determine FM 2 Hz and AM 20 Hz sensitivity thresholds.

A genome scan for loci shared by autism spectrum disorder and language impairment.

Objective: The authors conducted a genetic linkage study of families that have both autism spectrum disorder (ASD) and language-impaired probands to find common communication impairment loci. The hypothesis was that these families have a high genetic loading for impairments in language ability, thus influencing the language and communication deficits of the family members with ASD. Comprehensive behavioral phenotyping of the families also enabled linkage analysis of quantitative measures, including normal, subclinical, and disordered variation in all family members for the three general autism symptom domains: social, communication, and compulsive behaviors.

Gene × gene interaction in shared etiology of autism and specific language impairment.

Background: To examine the relationship between autism spectrum disorders (ASD) and specific language impairment (SLI), family studies typically take a comparative approach where families with one disease are examined for traits of the other disease. In contrast, the present report is the first study with both disorders required to be present in each family to provide a more direct test of the hypothesis of shared genetic etiology.

Methods: We behaviorally assessed 51 families including at least one person with ASD and at least one person with SLI (without ASD).

Genetic covariation underlying reading, language and related measures in a sample selected for specific language impairment.

Specific language impairment is a developmental language disorder characterized by failure to develop language normally in the absence of a specific cause. Previous twin studies have documented the heritability of reading and language measures as well as the genetic correlation between those measures. This paper presents results from an alternative to the classical twin designs by estimating heritability from extended pedigrees.

Combined linkage and linkage disequilibrium analysis of a motor speech phenotype within families ascertained for autism risk loci.

Using behavioral and genetic information from the Autism Genetics Resource Exchange (AGRE) data set we developed phenotypes and investigated linkage and association for individuals with and without Autism Spectrum Disorders (ASD) who exhibit expressive language behaviors consistent with a motor speech disorder. Speech and language variables from Autism Diagnostic Interview-Revised (ADI-R) were used to develop a motor speech phenotype associated with non-verbal or unintelligible verbal behaviors (NVMSD:ALL) and a related phenotype restricted to individuals without significant comprehension difficulties (NVMSD:C). Using Affymetrix 5.

Increasing genotype-phenotype model determinism: application to bivariate reading/language traits and epistatic interactions in language-impaired families.

While advances in network and pathway analysis have flourished in the era of genome-wide association analysis, understanding the genetic mechanism of individual loci on phenotypes is still readily accomplished using genetic modeling approaches. Here, we demonstrate two novel genotype-phenotype models implemented in a flexible genetic modeling platform. The examples come from analysis of families with specific language impairment (SLI), a failure to develop normal language without explanatory factors such as low IQ or inadequate environment.

Associations between the size of the amygdala in infancy and language abilities during the preschool years in normally developing children.

Recently, structural MRI studies in children have been used to examine relations between brain volume and behavioral measures. However, most of these studies have been done in children older than 2 years of age. Obtaining volumetric measures in infants is considerably more difficult, as structures are less well defined and largely unmyelinated, making segmentation challenging.

Using early standardized language measures to predict later language and early reading outcomes in children at high risk for language-learning impairments.

The aim of the study was to examine the profiles of children with a family history (FH+) of language-learning impairments (LLI) and a control group of children with no reported family history of LLI (FH-) and identify which language constructs (receptive or expressive) and which ages (2 or 3 years) are related to expressive and receptive language abilities, phonological awareness, and reading abilities at ages 5 and 7 years. Participants included 99 children (40 FH+ and 59 FH-) who received a standardized neuropsychological battery at 2, 3, 5, and 7 years of age. As a group, the FH+ children had significantly lower scores on all language measures at 2 and 3 years, on selected language and phonological awareness measures at 5 years, and on phonological awareness and nonword reading at 7 years.

Functional connectivity of the sensorimotor area in naturally sleeping infants.

Patterns of cortical functional connectivity in normal infants were examined during natural sleep by observing the time course of very low frequency oscillations. Such oscillations represent fluctuations in blood oxygenation level and cortical blood flow thus allowing computation of neurophysiologic connectivity. Structural and resting-state information were acquired for 11 infants, with a mean age of 12.

Assessment of functional development in normal infant brain using arterial spin labeled perfusion MRI.

Arterial spin labeled (ASL) perfusion MRI provides a noninvasive approach for longitudinal imaging of regional brain function in infants. In the present study, continuous ASL (CASL) perfusion MRI was carried out in normally developing 7- and 13-month-old infants while asleep without sedation. The 13-month infant group showed an increase (P<0.

Links between abnormal brain structure and cognition in holoprosencephaly.

Converging information on medical issues, motor ability, and cognitive outcomes is essential when addressing long-term clinical management in children with holoprosencephaly. This study considered whether adding more informative structural indices to classic holoprosencephaly categories would increase prediction of cognitive outcomes. Forty-two children with holoprosencephaly were examined to determine the association of deep gray nuclei abnormalities with cognitive abilities and the effect of motor skill deficits on cognitive performance.

Auditory event-related responses in children with semi-lobar holoprosencephaly.

The purpose of this study was to evaluate auditory sensory and discrimination responses in children with semi-lobar holoprosencephaly (HPE). Event-related potential (ERP) signals were recorded to tone pair stimuli at 62 electrode sites from the scalp using an oddball paradigm (a two-block design, inter-stimulus interval=70 or 300 ms; frequency of tone pair=100 vs. 100 Hz for the frequent and 100 vs.

The Carter Neurocognitive Assessment for children with severely compromised expressive language and motor skills.

In this paper, different means of assessing cognitive development in children with severe impairments in both their expressive language and their motor skills are reviewed. A range of techniques are considered, including traditional cognitive tests and behavioral and physiological measures, but these techniques are generally impractical and minimally informative when it comes to assessing children with both motor and speech impairments. Electrophysiological measures show some promise for the future, but are currently inadequate for wide-ranging cognitive assessment.

Examination of potential overlap in autism and language loci on chromosomes 2, 7, and 13 in two independent samples ascertained for specific language impairment.

Specific language impairment is a neurodevelopmental disorder characterized by impairments essentially restricted to the domain of language and language learning skills. This contrasts with autism, which is a pervasive developmental disorder defined by multiple impairments in language, social reciprocity, narrow interests and/or repetitive behaviors. Genetic linkage studies and family data suggest that the two disorders may have genetic components in common.

Specific language impairment in families: evidence for co-occurrence with reading impairments.

Two family aggregation studies report the occurrence and co-occurrence of oral language impairments (LIs) and reading impairments (RIs). Study 1 examined the occurrence (rate) of LI and RI in children with specific language impairment (SLI probands), a matched control group, and all nuclear family members. Study 2 included a larger sample of SLI probands, as well as their nuclear and extended family members.

A major susceptibility locus for specific language impairment is located on 13q21.

Children who fail to develop language normally-in the absence of explanatory factors such as neurological disorders, hearing impairment, or lack of adequate opportunity-are clinically described as having specific language impairment (SLI). SLI has a prevalence of approximately 7% in children entering school and is associated with later difficulties in learning to read. Research indicates that genetic factors are important in the etiology of SLI.